This is a summary list of all resource providers at University of Pennsylvania . The list includes links to more detailed information, which may also be found using the eagle-i search app.
The Abramson Cancer Center (ACC) is a dynamic, NCI-approved, comprehensive cancer center. Our dedicated members share the common goal of eliminating pain and suffering due to cancer. The ACC awards grants to cancer researchers, provides the necessary infrastructure for the conduct of cancer research (including the conduct of cancer clinical trials), and sponsors events and seminars of interest to cancer researchers.
The goals of the Acute Care Biobanking Core are to encourage and facilitate microbiome-focused research in the pathogenesis, diagnosis and treatment of patients with critical illness. Many patients who are critically ill are subject to processes and complications with microbially-driven or infectious mechanisms. The Core will assist in research by providing de-identified samples with linked clinical metadata to support research in this area.
Located on the first floor of the Towne engineering building, the AddLab houses the mechanical engineering department's 3D printers and post-processing equipment. The lab is generally staffed by student additive manufacturing assistants who are available to consult with members of the university on their 3D printing needs. The lab is restricted to approved workers who print and process all of the parts. If your interested in having anything 3D printed, please see our 3D printing page.
The PMI has assembled a unique combination of microscopes for single-molecule-imaging and single-molecule-force measurements. Secured through funding from the NSF, NIH, NIST, University Research Foundation and PSOM, these state-of-the-art instruments are being used to address important biological questions, using purified macromolecules and in live cells. The instruments are only the starting point, as PMI investigators develop novel imaging technologies that will greatly impact future research and funding. Available directly to the Penn community are:
1) Optical tweezers instruments for the measurement of nanometer-scale displacements and picoNewton-scale forces, both used for measuring biological forces and manipulating objects in vitro and in the cytoplasm of live cells.
2) A Bruker Catalyst Atomic-Force-Microscope (AFM) for measuring nanoNewton-scale forces, and for imaging microfabricated surfaces.
The laboratories of PMI members also develop and utilize advanced technologies for measuring macromolecule dynamics and localization that may be accessed via collaboration. Unique multiwavelength total internal reflection fluorescence (TIRF) microscopes provide millisecond-scale temporal and nanometer-scale spatial resolution of fluorescent molecules (e.g., GFP-proteins & quantum dots) in vitro and in vivo. In addition, polarization optics allow conformational changes to be observed in single molecules.
Research in my laboratory focuses on the interrelationship between energy stores and regulation of energy balance by the brain. Contrary to the prevailing view of the adipocyte as merely a specialized cell for the storage of excess energy in the form of triglycerides, there is increasing evidence that adipose tissue plays a more active role in energy homeostasis. The levels of leptin, adiponectin, resistin and other hormones secreted by adipose tissue are dependent on the status of energy balance, and serve as important signals linking energy stores to peripheral and central homeostatic mechanisms. Adipokines also have profound effects on the neuroendocrine axis, and glucose and lipid metabolism.
Immuno-gene Therapy for Thoracic Malignancies
Lung cancer and other thoracic malignancies are the leading cause of cancer deaths in the United States today. The Thoracic Oncology Research Laboratory is focusing on the design of new treatment strategies for lung cancer and mesothelioma based on the rapidly evolving disciplines of molecular biology, immunotherapy, and gene therapy.
Dr. Albelda’s research is translational in focus and includes animal models, work with human tumor samples, and the conduct of clinical trials. This work is primarily funded through a recently renewed Program Project from the National Cancer Institute and participation in a number of RO1 grants.
The tumor microenvironment is one area of active study. Studies are underway with the goals of 1) a better understanding of the biology of the tumor microenvironment with a focus on the immunuosuppressive activities of white blood cells and fibroblasts, 2) novel approaches to alter the tumor microenvironment to enhance immunotherapy including studying effects using COX-2 inhibitors, TGFbeta inhibitors, T-regulatory cell inhibitors., antibodies against B-cells, and chemotherapeutic drugs. A second area of interest in the lab is the use of adoptive T cell transfer to treat lung malignancies. Studies are underway to modify T cells in order to make them traffic more efficiently into tumors, to have better killing function, and to resist inactivation by the tumor microenvironment. A T cells targeting cancer-associated fibroblasts is being developed. In addition, Dr. Albelda is closely involved with a number of immunogene clinical trials at Penn using an adenovirus expressing the immune-activator interferon-alpha that is instilled into the pleural space of mesothelioma patients (in collaboration with Dr. Daniel Sterman) and T cells altered to attack the mesothelioma tumor target, mesothelin (in collaboration with Drs. Carl June and Andrew Haas).
The Alzheimer's Disease Genetics Consortium is funded by a grant from the National Institute on Aging (PI, Gerard D. Schellenberg; UO1AG032984), an $18.3 million five-year research grant to conduct genome-wide association studies (GWAS) to identify genes associated with an increased risk of developing late-onset Alzheimer’s disease (LOAD).
The Atchison laboratory is interested in determining the molecular mechanisms responsible for transcriptional regulation and the control of B cell development. To pursue these studies, we explore the functions of a number of transcription factors that regulate immunoglobulin gene expression and that play important roles in immunoglobulin locus structure, antibody maturation, lineage differentiation, and oncogenesis. We pursue our studies by biochemical, molecular biological, genetic, and developmental approaches using a variety of experimental systems including cell lines representing defined stages of B cell development, multipotential tumor lines, transgenic animals, and chimeric mice. General areas of current interest include:
1. Developmental control of immunogloblulin locus structure. Transcription factor YY1 is crucial for B cell development, and we found this factor can regulate immunoglobulin kappa V gene rearrangement and repertoire. Current data suggest that YY1 binds to numerous locations within the kappa locus and associates there with Polycomb Group, Condensin, and Cohesin proteins. We speculate that YY1 nucleates the binding of these factors to the kappa locus in a tissue-specific and developmental stage-specific fashion.
2. Mechanism of antibody maturation. Within germinal center cells antibody genes undergo somatic maturation processes involving class switch recombination and somatic hypermutation. Both of these processes require the enzyme, Activation Induced Deaminase (AID). Levels of AID in the nucleus are very tightly regulated and misregulation of AID leads to B cell lymphoma. We found that transcription factor YY1 can physically interact with AID leading to increased nuclear stability and increased class switch recombination. We are currently studying the mechanism of this stabilization, and the role of YY1-AID interaction in B cell lymphoma.
3. Function of the transcription factor YY1 as a Polycomb-Group protein in transcriptional repression and embryonic development. We found that human YY1 can function as a Polycomb protein in vivo to repress transcription and to control embryonic development. YY1 also recruits other PcG proteins to DNA resulting in specific histone post-translational modifications. We are studying the mechanism of this recruitment and specific proteins that bridge YY1 to the Polycomb Group complex repressor proteins.
4. Function of YY1 in B cell lymphomagenesis. Physical interaction of YY1 with AID may augment its role in germinal center derived B cell lymphomagenesis. We are using mice that spontaneously develop B cell lymphoma to determine the impact of YY1 overexpression and YY1 loss on lymphomagenesis and agressiveness.
5. Role of transcription factor PU.1 in hematopoietic development and enhancer chromatin structure. We found that PU.1 binds to immunoglobulin enhancers and recruits other proteins to DNA. Using PU.1 conditional knock-out mice and a variety of PU.1 mutants that ablate specific functions, we are exploring the role of PU.1 in enhancer chromatin structure, protein recruitment to DNA, and B cell development.
ACARD (Automated Claims and Medical Record Databases) is a core in the Center for Clinical Epidemiology and Biostatistics (CCEB) created to foster epidemiologic research into therapeutics, using large population-based automated claims databases (Medicaid / Medicare) and medical records databases (GPRD™ and THIN), and an adverse event reporting system (AERS) database.
• Encourage investigators with diverse training to conduct studies focused on translational therapeutics and drug safety
• Provide access to large databases that allow for rapid and cost-effective research on therapeutics and drug safety
• Foster collaboration with CTSA sites outside of Penn who wish to use these databases for clinical research
Our research focuses on developing mouse models of stress sensitivity related to neurodevelopmental and neuropsychiatric disease. We utilize genetic and prenatal manipulations to elucidate mechanisms contributing to disease predisposition.
We have focused on utilizing approaches that range from fetal antecedents in programming of long-term disease risk to genetic targeting of cell type specific knockout mice.
We have focused on developing models of disease including affective disorders and obesity utilizing approaches that range from fetal antecedents, involved in programming of long-term disease risk, to genetic targeting of cell type specific knockouts.
We have initiated multiple lines of investigation that will provide insight into the timing and sex specificity of early life events promoting disease susceptibility, the maturation of central pathways during key periods of development, and the epigenetic mechanisms involved in long-term effects following stress exposure.
The research in my laboratory focuses on the study of genomic imprinting and X inactivation in mice.
DNA double strand breaks (DSBs) are hazardous cellular lesions. Unfortunately, they also are very common. DSBs arise in every S phase through DNA replication errors and can be induced in any cell cycle phase by exogenous factors such as ionizing radiation or endogenous factors such as reactive oxygen species. When un-repaired or mis-repaired, DSBs can result in genomic instability that can lead to cell death or drive malignant transformation. Despite their danger, DSBs are a necessary part of biology. In this context, the induction and repair of DSBs within antigen receptor loci during V(D)J recombination and class switch recombination (CSR) is essential for development and function of an immune system capable of adapting and responding to a wide variety of pathogens. Cells have evolved efficient, specialized, and redundant mechanisms to sense, respond to, and repair DSBs. This generally conserved DNA damage response (DDR) integrates cell cycle progression and cellular survival to facilitate repair, or trigger apoptosis if damage is too severe. The physiological importance of V(D)J recombination and CSR control mechanisms has been demonstrated by the fact that defects in each can lead to immunodeficiency, autoimmunity, and lymphoma; while the immunological relevance of DDR control mechanisms has been illustrated by observations that deficiency of these can lead to immunodeficiency and lymphomas with antigen receptor locus translocations. One main research focus within the lab aims to elucidate molecular mechanisms through which the DDR maintains genomic stability and suppresses transformation in cells during V(D)J recombination, CSR, and DNA replication. Another research focus within the lab aims to exploit the knowledge and animal models gained through these studies to design, develop, and test novel treatments for cancer that are more effective and less toxic than current clinical therapies. A third research focus aims to elucidate the epigenetic mechanisms by which antigen receptor gene rearrangements are coordinated between homologous alleles and activated/silenced in a developmental stage-specific manner to maintain genomic stability and suppress cellular transformation during V(D)J recombination. Another research focus within the lab aims to test our hypothesis that the molecular mechanisms that control antigen receptor gene rearrangements and the cellular DDR co-evolved in lymphocytes to ensure development of an effective adaptive immune system without conferring substantial predisposition to autoimmunity or cancer upon the host organism.
Monell's Behavioral and Physiological Phenotyping Core provides training and research support in the behavioral and physiological phenotyping of rodents, including surgical and electrophysiological techniques utilized in rodent models. Core personnel offer expertise, instruction and equipment needed for methodologies common to research in the chemical senses, including preference tests, gustometers, olfactometers, LabMaster systems and metabolic cages.
The Behrens lab mainly focuses on dendritic cell biology and their function in normal and pathologic immune responses. In particular, we have developed an interest in Toll-like receptors (TLRs), a set of molecules on dendritic cells that recognize pathogens via common molecular motifs and initiate inflammatory responses. Within this theme of dendritic cell/TLR biology, the lab has two major arms of research:
1) TLR signal transduction ? TLRs have classically been thought to signal cells to generate inflammatory responses via two major signaling conduits, the MyD88 and TRIF pathways. However, there are many modifying and regulatory pathways that intersect with these tow major TLR signaling cascades. We are interested in probing the role of tyrosine phosphorylation events, mediated by Syk and the adapter protein Slp-76 in modulating TLR function in dendritic cells and macrophages.
2) Macrophage Activation Syndrome ? MAS is a rare, but fatal complication of a number of rheumatic, oncologic, infectious, and genetic disorders. In particular, 10% of patients with Systemic Juvenile Idiopathic Arthritis will develop fulminant, life-threatening MAS. The syndrome consists of a ?sepsis-like? clinical picture, and the pathologic hallmark of the disease is the hemophagocytic macrophage. These are macrophages, typically found in the bone marrow, that are phagocytosing other live hematopoetic cells such as red blood cells, platelets, or leukocytes. The pathoetiology of MAS in poorly understood, but is thought to be in part due to excessive CD8+ T-cell/antigen presenting cell (APC) interaction, resulting in overwhelming inflammation. While the T-cell determinants of this pathologic interaction have been reasonably well characterized, the APC side has not. Which APC plays a role in the disease, what APC inflammatory mediators, and what signal transduction pathways are critical to disease all remain unanswered and are potential areas of therapeutic development. Furthermore, the physiologic role of the hemophagocyte remains debated. We have developed a novel model of MAS in the mouse that does not depend on a genetic mutation but rather on repeated TLR stimulation, replicating the inflammatory environment seen in the rheumatic diseases associated with MAS. We have identified a complex network of cytokines, including IFNg and IL-10, and cell types that contribute to disease. We are currently working our the regulatory mechanisms behind these cytokines and cells to both provide insight into the fundamental immunology of MAS and develop novel therapeutics. We are also using transcriptome analysis to investigate the function of hemophagocytes to better understand their role in MAS.
The lab combines genomic and genetic data to computationally model RNA processing, followed by experimental verification to decipher post-transcriptional regulation, phenotypic diversity and disease
The Bioinformatics Core of the Institute for Biomedical Informatics (IBI) provides professional bioinformatics services, including data analysis and consultant to UPenn biomedical research community. The core is also dedicated to build efficient pipelines to handle various next-generation sequencing (NGS) data, generated within our NGS core or elsewhere.
The Bioinformatics Core is also supported by IBI members whose areas of expertise include NGS related algorithm development, human disease research (diabetes, cancer, Autism, Alzheimer’s disease etc.), functional genomics, medical informatics, statistics genetics, computational biology. We provide bioinformatics support for grant application in all biomedical areas by drafting approaches, and offering computation resources and expertise for the proposed research.
The mission of the Bioinformatics Facility is to support the continuing research and education mission of The Wistar Institute and to grow and evolve in response to emerging research needs.
The Bioinformatics Facility is located in the Center for Systems and Computational Biology, which provides a state-of-the-art server room, office space, and educational and conference room space. The Facility provides Cancer Center investigators with database management, software application support, expertise in statistical analyses and computational modeling of biomedical research data and has recently grown to include statistical specialists and programmers as well as computational biologists. The Facility is supported and advised by members of the Center for Systems and Computational Biology.
Functions of the Facility reflect the research requirements of the three Cancer Center programs and are broadly divided into three areas: (i) data-management; (ii) statistical analyses and computational modeling; and (iii) advanced bioinformatics tools for integrative cancer biology. Typical data analyses include large scale information datasets (omics data), generated by high-throughput technologies addressing the following complex area:
• Genome sequencing (alternate splicing, RNA editing, mutation detection)
• Gene regulation (ChIP-chip, ChIP-seq, epigenetic profiling, promoter methylation arrays)
• Biomarkers (e.g. mRNA and miRNA microarray expression data)
• Proteomic analyses (mass spectrometry-based spectra, LCMS, DIGE, etc.)
• Polymorphism genotyping (e.g. Single Nucleotide SNP and Copy Number variations CGH, LOH).
The Facility has placed a high priority on integrating cancer research information representing a variety of data types, including clinical data, microarray data, massively-parallel sequence data, protein data, RT-PCR and functional assays. Data security is a primary focus of the Bioinformatics Facility in designing and implementing software systems.
The Biological Chemistry Resource Center (BCRC) at the Department of Chemistry has been established to provide an open access user facility for state-of-art biophysical analytical instrumentation. The goal of the center is not only to provide access to instrumentation, but also supply the graduate student and post-doc user community with a firm understanding of the scientific principles behind the techniques and on-site expertise to ensure successful experimentation. Instrumentation access will be available to the entire University of Pennsylvania research community.
The Biomechanics Core works with ITMAT faculty from Penn, ITMAT partner institutions, and members of the ITMAT Program in Translational Biomechanics."
"Consultation and initial pilot experiments performed with the Biomechanics Core are free-of-charge to ITMAT faculty from Penn, ITMAT partner institutions, and members of the ITMAT Program in Translational Biomechanics.
The Biorepository Core collects and organizes biospecimens from investigators across the Research Institute. With a capacity for approximately 7 million samples, the facility is designed to house all of the biospecimens available at Children's Hospital, avoiding specimen duplication, preserving precious materials, and providing broad access to data and materials. Initial sample collection will focus on DNA samples, but with the addition of other freezers in the near future, the facility can also safely store fluids, RNA, tissue samples, and a number of other biospecimens.
The Biostatistics Analysis Center (BAC) provides biostatistical and epidemiological consulting services to the University of Pennsylvania Health System research community. The BAC is staffed by professionally trained biostatisticians, biostatistical programmers, Geographical Information Systems (GIS) experts, data managers, and data entry staff. Faculty oversight for the BAC is provided by members of the CCEB Biostatistics and Epidemiology Divisions, with leadership for daily operations provided by a dedicated staff-level director. Specifically, Warren B. Bilker, PhD, Professor of Biostatistics, and John T. Farrar, MD, PhD, Associate Professor of Epidemiology, are Faculty Co-Directors and Amy Praestgaard, MS, is the staff-level BAC Director.
• Request BAC statistical analysis, programming, GIS, or data management services by completing the CCEB Research Services Request Form.
• Request a BAC Statement of Work and budget for inclusion in a grant submission by completing the CCEB Grant Registration Form and indicate in the Collaborative Personnel and Resource Needs section that you require MS Biostatistician support.
The Biostatistics and Data Management Core (BDMC) at The Children's Hospital of Philadelphia (CHOP) supports investigators from virtually all subspecialties of pediatric medicine and supports studies ranging from small, narrowly defined basic science projects to large, multi-site clinical trials.
The Biostatistics and Data Management Core currently supports more than 50 funded studies and collaborates with investigators on numerous grant applications each year. The BDMC is staffed by a Scientific Director, Deputy Director, and data management/information technology managers, as well as approximately 20 additional staff members representing the disciplines of biostatistics, data management, information technology and administration. The BDMC is located on the CHOP campus (3535 Market Street), and is operated and supported by Westat, a large health research organization with extensive biostatistics, data management and information technology capabilities.
The ability to respond to nutritional stress is one of the most primitive adaptations that organism must accomplish. The pathways that alert the organism to an absence of food and initiate an appropriate response are remarkably well-conserved and involve such critical signaling molecules as the protein kinases Akt and AMP-activated protein kinase (AMPK) as well as nutrient sensors such as the carbohydrate response element binding protein (ChREBP).
The Birnbaum lab studies this complex biological response in two contexts: the initiation of cell growth after a transition from nutritional deprivation to abundance and the insulin-dependent redistribution of simple substrates into long-term energy stores. The latter process involves a number of distinct but interacting components such as glucose-stimulated insulin secretion, and the insulin-dependent acceleration of hepatic lipid synthesis and glucose uptake into adipocytes and muscle. Two aspects of the regulation of glucose transport by insulin, both of which are studied in the Birnbaum lab, are the way in which insulin regulates the movement of hormone-sensitive Glut4 glucose transporter from the inside of the cell to the plasma membrane, and the signaling pathway by which insulin accomplishes this. There are also a number of projects underway aimed at understanding how the evolutionarily conserved sensor of nutritional stress, AMP-activated protein kinase, regulates carbohydrate and fat metabolism. These fundamental biological problems are addressed using experiments performed in tissue culture cells, mice and the genetically tractable organism Drosophila melanogaster.
Research in our laboratory is heavily involved in the use of mass spectrometry for proteomics, lipidomics, and DNA analysis. We are particularly interested in determining the factors that control lipid hydroperoxide-mediated damage to DNA, RNA, and proteins. Methodology is being developed to characterize covalent modifications to these macromolecules using novel mass spectrometry techniques, determining how these can be evaluated as potential “biomarkers” of various physiological processes and disease states, and assessing how such processes can be prevented using novel pharmacological agents.
Our research focuses on the interplay of bacterial virulence mechanisms and host innate immune recognition strategies. We are interested in defining how bacterial pathogens are sensed by host cells, how this sensing contributes to antimicrobial immune defense, and how bacterial pathogens evade these innate immune recognition pathways.
The immune system utilizes two types of recognition strategies to detect microbes – membrane-bound pattern recognition receptors (PRRs), such as Toll-like Receptors, detect conserved microbial structures present in all microbes of a given class. Conversely, cytosolic receptors sense microbial virulence activities that result from the disruption of celluar processes or the inappropriate contamination of the host cell cytosol by microbial products. Notably, innate immune cells infected with a variety of unrelated bacterial pathogens, but not avirulent or non-pathogenic bacteria, undergo a pro-inflammatory form of cell death termed pyroptosis, which depends on the cellular protease caspase-1. Caspase-1 plays an important role in the cleavage and secretion of the pro-inflammatory cytokines IL-1ß and IL-18, and is therefore important in immune defense against various microbial infections. Members of the Nucleotide binding domain-Lecuine Rich Repeat (NLR) family of cytosolic signaling proteins recruit caspase-1 into multi-protein activating platforms termed ‘inflammasomes’. Inflammasome complexes are activated in response to a variety of bacterial, viral, and fungal infections and inflammasome activation plays an important role in host defense. However, successful pathogens have also evolved mechanisms to evade or subvert inflammasome activation, thereby avoiding caspase-1-dependent immune responses.
We use the Gram-negative bacterial pathogens Yersinia pseudotuberculosis and Salmonella typhimurium in combination with genetic, biochemical, and imunological approaches on both the bacterial and host side to understand the bacterial signals that trigger inflammasome activation, how inflammasome activation is coupled to innate and adaptive immune responses, and how bacterial pathogens evade inflammasome-dependent immune responses.
Recent studies in our laboratory have revealed unexpected links between caspase-1 activation and activation of other cell death pathways (Philip et al., PNAS 2014), and have identified a novel mechanism for sensing of TCA cycle metabolites by the NLRP3 inflammasome pathway (Wynosky-Dolfi et al., J Exp Med, 2014). Further studies have also demonstrated that bacterial pathogens tune the delivery of specific virulence factors into the host cell, so as to avoid triggering inflammasome response pathways (Zwack et al., MBio 2015)
Ongoing Projects in the Brodsky Lab involve (1) Dissecting the role of extrinsic cell death pathway components in inflammation. (2) Defining the contribution of inflammasome activation to anti-Salmonella immunity. (3) Determining the role of cell death in anti-bacterial immunity in vivo (4) Understanding the role of bacterial secretion system pore proteins in inflammasome activation
The focus of my lab is on the role of the cytoskeleton in T cell and dendritic cell function. The cytoskeleton is intimately involved in determining the efficiency and the fidelity of the immune response. For example, when a cytotoxic T cell recognizes a tumor cell for lysis, specific receptor interactions trigger capping of the cortical actin cytoskeleton, creating a specialized membrane domain that is important for T cell signaling events leading to lysis of the tumor cell. Similar processes are important for directing and modulating T cell help. In dendritic cells, actin regulatory proteins control the uptake and presentation of antigens, migration of antigen-bearing cells from sites of infection to lymphoid organs, and defining the outcome of T cell stimulation. Our long-term goals in the lab are to understand how receptor-ligand interactions at the cell surface trigger remodeling of the cytoskeleton, and how the cytoskeleton in turn affects the immune response. Proteins of current interest in the lab include WASP, an actin regulatory protein involved in immunodeficiency disease, HS1, a related protein implicated in autoimmune disease, and Crk family adapter proteins, proteins that control T cell adhesion and migration.
Research in the Bushman laboratory focuses on host-microbe interactions in health and disease, with particular focus on studies of 1) the human microbiome, 2) HIV pathogenesis, and 3) DNA integration in human gene therapy.
In recent years, our work has been driven increasingly by the remarkable new deep sequencing methods, which can produce more than 100 billion bases of DNA sequence information in a single instrument run.
For microbiome studies, this allows comprehensive analyze of microbial populations without reliance on culture-based methods, which can detect only a small fraction of all organisms present.
For studies of HIV replication, this allows analysis of complex viral populations or distributions of retroviral DNA integration sites in the human genome.
For gene therapy, this allows tracking of integrated vectors in gene-corrected subjects and molecular characterization of adverse events. Sample acquisition can sometimes be difficult in such projects, but bioinformatic analysis afterwards is almost always harder. We have been carrying out this type of study since 2002, when we showed that HIV DNA integration in human cells was favored in active transcription units, and over the years have built up partially automated software pipelines that allow efficient analysis deep sequencing data.
Lab members and collaborators cover a range of specialties, including clinical researchers, molecular biologists, computational biologists, and statisticians.
CARDIoGRAMplusC4D (Coronary ARtery DIsease Genome wide Replication and Meta-analysis (CARDIoGRAM) plus The Coronary Artery Disease (C4D) Genetics) consortium represents a collaborative effort to combine data from multiple large scale genetic studies to identify risk loci for coronary artery disease and myocardial infarction.
The CHOP Microbiome Center supports planning microbiome projects, DNA purification, library preparation, high throughput sequence analysis, and bioinformatic analysis of the output."
"To request pricing or core services, please complete this form and send to:
Jessi Erlichman firstname.lastname@example.org
Requests for pricing must be submitted at least 4 weeks prior to grant deadline.
The Behavioral Neurosciences Core provides consultation and assistance to investigators regarding psychological, neuropsychological, and psychiatric components of research studies involving pediatric subjects.
Together, the services provided by the Behavioral Neurosciences Core offer research infrastructure support across the entire process of research, from pre-design consultation to development and analysis of behavioral data, and across multiple domains of functioning and outcomes.
The Cardiovascular Phenotyping Unit provides cardiac testing services with shared facilities for both children and adults. The Unit provides the technical services and expertise to conduct the highest quality research, provides research tests in a cost-effective manner, and provides unparalleled training opportunities in clinical research for investigators, fellows, students and technicians. Most services are provided across the life cycle. For studies involving both adult and pediatric populations, the pediatric and adult CPUs can collaborate closely and standardize procedures according to the investigators’ needs. Please contact the Directors for special arrangements or input regarding cardiovascular phenotyping.
The Exercise Medicine Unit offers exercise training and testing services. The exercise training room contains:
• arc trainer,
• recumbent bike,
• functional trainer,
• adjustable bench,
• and a power block area.
It is staffed by a full-time, certified exercise trainer who can help design exercise training protocols and administer them to clinical research study participants. Exercise interventions can be designed to occur onsite at the Mutch building or for community/home settings. Consultations to assist with design of exercise intervention protocols are available.
Exercise testing services include a recumbent exercise bike and a motorized treadmill, with adjacent ECG monitoring, metabolic cart and VO2 max measurements, and anaerobic power testing. Additional testing services include grip strength, six minute walk tests, and gait speed. Objective Physical Function tests (e.g. SPPB, TUG, and PPT) can also be done by the staff of this unit. Consultations to assist with designing exercise testing protocols are available.
The staff of this core gives guidance and/or coordinates data management, capture and analysis on behalf of the investigator within the Institute and assists more broadly with computing issues related to the approved protocol. This core provides services to investigators for their CTRC-approved studies that are utilizing other CTRC core services.
Nutrition plays a vital role in health at all ages. The Clinical and Translational Research Center offers a Bionutrition Research Unit (BRU) to facilitate and implement clinical and translational research services. Research dietitians assist investigators with research design, implementation, data collection and analysis in study protocols.
The Dietary Assessment Unit of the Nutrition Core provides a broad range of nutrition-related research services to investigators at the Children's Hospital of Philadelphia, the Hospital of the University of Pennsylvania (HUP) and Penn Presbyterian Medical Center (PMC).
The Nutrition Assessment Unit of the Nutrition Core is a state-of-the-art facility for the assessment of growth and body dimensions, body composition (the amount of muscle, fat and bone in the body), energy expenditure, bone density, and muscle strength. The Unit has two locations and four experienced technicians for performing research assessments.
The Clinical and Translational Research Center (CTRC) offers ophthalmological testing services for children. The Ophthalmology Core at CHOP’s CTRC was established to provide clinical and translational research services in ophthalmology for the assessment of visual function and structure.
Services provided include:
• Eye exams (includes visual acuity, recognition acuity, grating acuity, motility, slit lamp exam / anterior segment evaluation,
external segment evaluation, fundus exam, refraction, best corrected)
o Contrast sensitivity
o Color vision testing
• Optical coherence tomography (OCT) tests of the:
o Anterior segment
o Posterior segment – optic nerve
o Posterior segment – retina
• Visual field measures:
o Using Humphrey
o Using Goldman
• Full field sensitivity testing
• Visual evoked potential
• Fundus photography
• Ocular ultrasound
• Professional interpretation of all tests is also available
The Clinical and Translational Research Center (CTRC) has two main locations as well as satellite locations. The protocols cover a wide variety of research areas including: HIV, sleep disorders, cholesterol, obesity, diabetes, various cancers, arthritis, hypertension, renal disease, short bowel syndrome, and neonatal and surgical studies as well as new treatments for various diseases. The CTRCs service over 1200 inpatients and over 6000 outpatients a year. Research subjects range from premature infants to the elderly, with the majority of adults being seen at HUP.
HUP Unit - Dulles Building:
• 8 bed inpatient
• 8 chair and 2 bed outpatient unit
• metabolic kitchen
• Scatterbed nursing services throughout hospital units including the ICUs, ED and operating rooms
UPPMC Unit – 1st Fl Mutch Building:
• 18 outpatient treatment beds
• metabolic kitchen
• 4 bed inpatient unit – 5 West Main
• outpatient unit with 2 treatment rooms, 4 treatment chairs and a consultation room - Main 7
• Scatterbed nursing services in Newborn Nursery - Ravdin Building
The nurse manager should be contacted prior to submitting a new protocol submission to the CTRC and discussions should continue throughout the start-up process.
The CTRC Sleep Core provides services in support of clinical sleep research. It is based at two sites: the CHOP Sleep Laboratory, convenient to the CTRC Outpatient Facility on the 7th Floor of Main Hospital and the University of Pennsylvania’s Sleep Laboratory, located on the 11th Floor of the Gates Building which is part of the medical complex of the Hospital of the University of Pennsylvania. The Sleep Core contains a total of six designated research beds, dedicated staff, and state-of-the-art equipment that provides support for a variety of sleep-related research initiatives. Studies performed in the Sleep Core include overnight polysomnography, multiple sleep latency testing, neurobehavioral testing and actigraphy. The Sleep Core´s goals include providing highest-quality sleep studies, extending sleep research to disciplines not traditionally involved in this area, further developing extant multidisciplinary programs, and offering training opportunities for medical students, residents, fellows, and junior faculty in clinical sleep research. The Sleep Core is associated with CHOP’s and UPHS’ American Academy of Sleep Medicine-accredited Sleep Center Laboratories.
Services for pediatric and adult subjects:
Multiple Sleep Latency Testing
Sleep Core Library
The Study Design and Biostatistics (SDAB) Core works closely with existing resources to provide targeted study design and biostatistics support to ITMAT/CTSA investigators. The Core serves as a direct provider of services, including protocol review, study design, proposal development, and performance of simple to potentially substantial complex analyses. SDAB integrates the support available with the HUP and CHOP Clinical and Translational Research Centers (CTRCs), the expertise and resources of faculty in the Center for Clinical Epidemiology and Biostatistics / Department of Biostatistics and Epidemiology (CCEB/DBE), the Biostatistics Analysis Center (BAC), and the Biostatistics and Data Management Core (BDMC) at CHOP.
The Translational Core Laboratory consists of the Specimen Collection, Processing and Point of Care, Biochemistry, Cell Culture/DNA Isolation, and Molecular Biology core laboratories. Laboratory testing is integrated across Penn and CHOP, and TCL services are provided at multiple physical locations at both Penn and CHOP.
Penn location: first floor Smilow Center for Translational Research
CHOP location: 804 Abramson Research Center (ARC)
The Cancer Histology Core is a non-profit, research-oriented resource core supported by the Abramson Cancer Center. It offers all histology-related services to all members of the Abramson Cancer Center with high quality, low cost, fast turnout, and easy interaction.
Service will be open to all life sciences investigators at Penn, but priority will be given to full members of the Abramson Cancer Center.
The CML specializes in applying geographic information systems (GIS) software and hardware to digitally link data and geography to generate spatial databases, maps, spatial statistical analyses, and mapping applications, providing a useful way to reveal spatial and temporal relationships among data.
By using GIS to visualize geographic relationships that affect health outcomes, public health risks, disease transmission, access to health care, and other public health concerns, the CML conducts spatial research, policy analysis, and develops mapping applications of value to investigators at Penn and beyond.
Cell Center Services Facility is the service component of the Cell Center, provides training and services in various cell culture and associated procedures including Mycoplasma and Endotoxin testing. The cell culture service includes cell culture at various scales, large scale growth of hybridoma and other cell lines followed by antibody purification by protein G column and the generation of lymphoblastoid cell lines by EBV induced transformation of lymphocytes. In addition, the facility prepares specialized cell culture media, drosophila media, and various molecular biological reagents.
Recently cell transfection and selection service has been introduced at the facility.
The Cell Center Stockroom is a division of the Genetics Core Facilities (GCF). The GCF is a University service center, established in 1973 to provide consultation, training, and services in the areas of cell culture and hybridomas. Also, the GCF to provides a full range of cell culture media and molecular biology reagents needed by investigators to perform cell culture techniques in their own laboratories. The DNA Sequencing Facility, Genetic Diagnostic Laboratory and Transgenic/Chimeric Animal Facility are the remaining three divisions of the GCF.
The Stockroom serves University of Pennsylvania investigators and affiliate institutions (Cancer Center, Chidren's Hospital of Philadelphia, Hospital of the Unviersity of Pennsylvania, The Wistar Institute, Monell Chemical Senses Center, and Presbyterian Hospital) by coordinating relations with various suppliers of molecular biological research materials. This involves not only bulk purchasing of these products, but the negotiation of discounts and convenient delivery arrangements. There are over 1,100 products on-site for immediate delivery in the Stockroom. Special ordering of non-regularly stocked products is available from 28 bioreagent vendors with discounted pricing and overnight delivery.
List of Stockroom Vendors:
Cell Center Services
Cell Signaling Technologies
Fisher (Thermo) Scientific
Integrated DNA Technologies Invitrogen
New England Biolabs
Perkin Elmer Life Sciences
WorldWide Medical Products
The CDB Microscopy Core is the primary light microscopy facility for researchers at the Perelman School of Medicine at The University of Pennsylvania. We are also open to the entire University of Pennsylvania community as well as to CHOP, Wistar, and other local institutions. While our emphasis is on confocal and related technologies, our aim is to provide personalized assistance on all aspects of imaging, from tips on sample preparation to training on one of our microscopes to processing and analysis of image data.
Radiologists, physicists, and technologists help researchers utilize the resources available within the Department of Radiology at the University of Pennsylvania. Our mission is to oversee proposed research protocols that involve human, animal, phantom or specimen studies in an effort to achieve two goals:
• To ensure that all research performed on the CT scanners comply with CACTIS and University policy, and Federal Regulations
• To determine if CACTIS can maintain the resources required to carry out each research protocol, including personnel, software, hardware and scan time
Under the direction of the Chair, Dr. Harold Litt, the CACTIS committee reviews proposed research requests and makes decisions and recommendations accordingly.
• Oversees the day-to-day operations of all CT procedures associated with research protocols
• Provides information regarding the use of the CT facilities to the research community at the University of Pennsylvania
• Provides CACTIS users with all of the policies of the institution governing research
• Ensures that CACTIS is in compliance with these policies
The overall mission of CAMRIS is to provide oversight in the responsible use and application of Magnetic Resonance in research through leadership, education, and guidance. These principles are manifest in the development of new research and collaborations inside and outside the Radiology Department which can translate into advanced clinical techniques; training in safe and efficient use of this investigative tool and dissemination of current, accurate and evolving MR Technology; scheduling upgrades of MR Systems and facilities; scheduling systems operations and personnel within the MR department; and receiving and acting on recommendations pertaining to the administration of CAMRIS Facilities.
Center for Advanced Retinal and Ophthalmic Therapeutics (CAROT) was established to advance the development of novel biologic and small molecule therapeutics for retinal and ocular diseases through a balanced commitment to basic research, translational development, and the clinician/patient communities. With a solid foundation of clinically relevant ocular research, CAROT positions itself as a global premiere center for translating novel bench research, such as gene and cell therapies, into the clinics and the market. The center leads, consults and collaborates on projects at all stages of clinical development. We aim to establish an efficient and effective translational infrastructure, and foster a supportive environment for both academic and commercial communities.
To achieve our center mission, we have established a number of core facilities that are available to our collaborators and colleagues.
CAG offers next-generation sequencing (NGS), SNP genome wide association study (GWAS), and a range of other services.
The CBI is a type 1 center within Radiology and coordinates the translational bioimaging center of the Institute for Translational Medicine and Therapeutics (ITMAT). The CBI is organized into a Basic Imaging Research Division, Translational Research Division, and imaging Core Facilities supported by the CBI Administration. Although initially the CBI will focus primarily on in-vivo imaging, it is appreciated that tissue analysis including digital pathology and molecular diagnostics share many of the same technical challenges and we would expect to engage the pathology and cellular imaging community over time.
The Center for Injury Research and Prevention is dedicated to advancing the safety and health of children, adolescents, and young adults through comprehensive research resulting in practical tools to reduce injury and promote recovery.
To advance science and create tangible impact, the Center:
Addresses children's injuries comprehensively - from before-the-injury prevention to after-the-injury healing
Translates rigorous scientific research to usable, age-appropriate tools and practical steps for families, professionals, and policymakers
Asks and answers important questions from an interdisciplinary perspective, with expertise in Behavioral Sciences, Clinical * Care, Engineering, Epidemiology and Biostatistics, Human Factors, Public Health and Communications
Engages with a broad range of organizations from universities and government entities to non-profit groups, foundations and corporations, to ensure that research results extend to the real world
CIRP turns "research into action" by determining priorities for pediatric injury research, establishing key collaborations and networks to apply that research, and providing education, training and professional development across three injury science disciplines: Behavioral Science, Engineering, and Epidemiology and Biostatistics. The Center also utilizes Outreach and Dissemination to translate the research across these disciplines into real-world applications.
The Center for Pharmacoepidemiology Research and Training (CPeRT) was founded in 2012 as a center within the Center for Clinical Epidemiology and Biostatistics (CCEB). Its mission is to:
• Provide an intellectual home for pharmacoepidemiology at Penn
• Promote the conduct of applied and methodologic pharmacoepidemiology research
• Foster training of the next generation of pharmacoepidemiologists
• Expand number of Penn faculty members performing pharmacoepidemiology research
CPeRT members are leaders in the development and use of large administrative and medical record databases for studying drug effects. CPeRT is a center within the Developing Evidence to Inform Decisions about Effectiveness (DEcIDE) Network funded by the Agency for Healthcare Research and Quality, and a center in the FDA-funded Scientific Program to Support Epidemiology Investigations. CPeRT members also edit Pharmacoepidemiology, 5th edition and Textbook of Pharmacoepidemiology.
The Wistar Institute’s Center for Systems and Computational Biology (CSCB) is an interdisciplinary unit that applies advanced computational and technological systems to the understanding of human disease. Through the CSCB, Wistar scientists are developing lifesaving tests and therapies for a variety of diseases, including cancer, cardiovascular disease, and HIV/AIDS.
The CSCB meets a pressing need among researchers. In the decade since the Human Genome Project first published the sum total of genes carried in our DNA, scientists have come to an even greater appreciation of the complexity of life. They understand that states of both health and disease are dictated by the intricate relationships between genes, proteins, cells, and entire groups of cells.
Through the Center, Wistar scientists can take complicated sets of data and boil them down to their essential nature, highlighting distinct points amid these tangled, interrelated genetic systems where therapeutic treatments will have the most effect.
The ultimate result will be improved targeted drugs; better biomarkers that will enable efficient tests for disease diagnosis, patient prognosis and predictions for a patient’s response to treatment; and a deeper understanding of the biology of life.
The mission of the CEET is to determine the mechanistic links between environmental exposures and diseases of environmental etiology. Understanding these processes can lead to early diagnosis, and prevention strategies. The overall goal is to improve environmental health and medicine in our urban region. Many of the solutions to the problems in this region will be translatable to other urban regions both nationally and globally.
This Research Core will provide training, advice and research support in molecular biological techniques used to analyze gene expression in cell culture and manipulate the genomes of rodent model organisms. The Core will centralize labor-intensive construct generation common to multiple users and provide users with technical expertise in molecular biological manipulations both in vitro and in vivo. The Core facility has all equipment, reagents, and expertise needed to carry out the following manipulations of RNA, DNA, and protein: RNA isolation, cDNA production, antisense RNA amplification, cloning, subcloning, recombineering, gel electrophoresis, transfection and tissue culture.
The Clinical Cell and Vaccine Production Facility (CVPF) renders bench-to-bedside translational medicine a reality. Equipped with state of the art facilities, the CVPF manufactures cell and gene biotherapeutics and is accredited by the Foundation for the Accreditation of Cellular Therapy (FACT). Further, the CVPF is the only GMP (good manufacturing practices) compliant facility on campus and functions as an NCI approved Abramson Cancer Center (ACC) Shared Resource. As an ACC Shared Resource and Path and BioResources core facility, the CVPF supports numerous investigational new drug (IND) protocols. Current protocols target a variety of disease indications (primarily HIV, adult and pediatric cancers, and stroke); many more trials are in development and, once approved, will further expand the scope of diseases targeted for cell and gene therapy. For more information on current trials, explore our “Clinical Trials” page.
The Clinical Research Computing Unit (CRCU) is an Academic Clinical Research Organization within the Center for Clinical Epidemiology and Biostatistics (CCEB) in the Perelman School of Medicine at the University of Pennsylvania. Since its inception in 1997, the CRCU has been expertly providing the full range of services essential for the conduct of clinical research projects, including Phase I-IV, multi-center, randomized, clinical trials, registry, and cohort studies utilizing state-of-the-art technology and tools to ensure superior data quality. The CRCU provides expertise in project management, data coordination and research computing tailored to meet your project requirements. The CRCU project teams partner with the BAC in the project design phase to plan accurate and precise data collection modules and to structure project reports for steady oversight. We specialize in study design and development, site management and training, data collection, processing, quality control, regulatory requirements and reporting, database development, administration, security, data storage and proposal development.
The Clinical Research Support Office (CRSO) is the central office for clinical research support services at CHOP. The CRSO provides leadership, administrative guidance, and support services to support both novice and experienced clinical investigators with investigator-initiated and industry-sponsored research projects. The CRSO’s core services include clinical research professionals who support operationalizing clinical research projects. These services include RNs, CRCs, and PMs to operationalize and manage clinical research projects; regulatory affairs professionals to prepare, submit, and manage INDs, IDEs, and other submissions to regulatory agencies and committees; contracting and legal professionals to negotiate agreements in support of clinical research; recruitment and marketing professionals to work with investigators to strategize, develop, and implement marketing and recruitment plans to facilitate enrollment into clinical research projects; and other business and administrative support.
The mission of the CRSO is to make it easier for the CHOP research community to conduct quality clinical research projects. The CRSO’s services include:
• Clinical research personnel (study coordinators, research nurses, program/project managers, clinical research supervisors) provide support to clinical investigators, enabling investigators to carry out all types of clinical research projects in a manner consistent with CHOP’s mission—excellent patient care, top-quality education, and innovative research. The CRSO assists with the start-up, execution, and completion of clinical research projects and ensures compliance with local and federal requirements. CRSO personnel are well-trained clinical research professionals who can be assigned to support any type of clinical research project.
• Regulatory affairs professionals provide regulatory guidance, operational support, and institutional oversight for clinical trials conducted under a CHOP sponsor-investigator IND/IDE. The CRSO also coordinates and submits regulatory correspondence to regulatory committees and agencies such as the IRB, FDA, and DSMBs.
• Contract administrators negotiate Clinical Trial Agreements (CTA) for industry-sponsored clinical research.
• Recruitment Enhancement Core (REC) collaborates with research teams to strategize, develop, and implement marketing and recruitment plans to increase enrollment into clinical research projects. The REC liaises with other clinical and research departments to leverage institutional biobanking and data repository resources with the goal of building a robust and efficient sample and data biorepository.
• Research navigation services guide and connect research personnel to answers, resources, and tools to facilitate clinical research. The navigator is available to assist investigators with any questions that arise during the design, start up, and execution of clinical research projects.
• Clinical research professionals will assist the research community with the development of clinical research budgets, operational review of investigator-initiated protocols, and other administrative-related activities.
Contact email@example.com with details for a fee quote.
The Clinical and Translational Research Center (CTRC) was formed with the receipt of the Clinical and Translational Science Award (CTSA), an NIH Roadmap initiative. The CTRC has child and adult specific components at the Children's Hospital of Philadelphia (CHOP) and University of Pennsylvania, respectively, as well as joint components. The CTRC merged the General Clinical Research Centers (GCRCs) at both institutions, and introduced new programs and services. The goal of the CTRC is to provide the resources, environment, operations, and training to support and promote high-quality clinical and translational research by qualified investigators.
The purpose of the Community Engagement and Research Core in the Penn CTSA is to facilitate community-based research and community engagement, especially community-based participatory research, and enhance the translation of research and technological developments to key public health and community stakeholders.
1. Foster community-based participatory research projects through developing training programs and integrating lectures into existing academic programs
2. Determine community health needs and priorities
3. Promote community-based research within the area of health disparities through seminar series
4. Continue the involvement in community outreach and education events to engage the community
5. Fund the conduct of CEAR Core pilot studies
6. Facilitate the use of academic-community partnerships to aid in the recruitment of subjects
To promote the use of Penn Health System information resources in support of clinical research.
1. Facilitate collection of data from operational information systems in the Penn health system
2. Facilitate the creation of interventions in operational information systems in the Penn health system
3. Foster the use of information systems such as electronic medical record and computerized order entry in the conduct of clinical trials
4. Enable the use of Electronic Health Records, Computerized Order Entry Systems, Health System Administrative Databases, laboratory and other ancillary test information systems to provide primary data for epidemiological and health services research studies
5. Educate ITMAT investigators on the types and quality of data and limitations of its use for health system information systems
The goal of our work is to help make sense of the enormous amount of biomedical data generated by high-throughput genomic approaches and synthesize them into something more than the sum of the parts. To that end, we are developing tools that enable researchers to mine and integrate data from a variety of different sources and types of experiments. In particular we are applying these approaches to expand our understanding in the areas of diabetes and infectious disease. We model data with networks and reality with ontologies especially the Ontology for Biomedical Investigations (OBI) for the latter.
Our research goal is to develop, evaluate and apply novel computational methods and open-source software for identifying genetic and genomic biomarkers associated with human health and disease. Our focus is on methods that embrace, rather than ignore, the complexity of the genotype-to-phenotype mapping relationship due to phenomena such as epistasis and plastic reaction norms. Areas of interest include artificial intelligence, bioinformatics, biomedical informatics, complex systems, computational biology, genetic epidemiology, genomics, human genetics, machine learning, and visual analytics.
Our education goal is to provide interdisciplinary training and research experience to undergraduate, graduate, and postgraduate students. Our philosophy is that biomedical researchers of the future need to speak multiple languages to effectively collaborate with diverse teams of people focused on solving the hardest problems in health and healthcare.
The Curran laboratory studies brain development and pediatric brain tumors. The goal is to identify molecular changes and potential drug targets. Additional studies focus on the mechanism of action of anticancer drugs in tumor cells and cancer models.
One of the cyclotrons is a Japan Steel Works (JSW) BC3015 30 MeV machine, capable of accelerating protons, deuterons, 3He, and 4He. Beam currents of 10-20 mA are typical with a maximum current capability of 60 mA. In 2009, an IBA 18/9 MeV Cyclone cyclotron was added into an expanded vault adjacent to the existing JSW cyclotron. The second cyclotron provides for higher beam currents than are available on the JSW cyclotron. As a result, the 18FF- production yield increases from 2 Ci to 12 Ci and; 11CCO2 yield increases from 3 Ci to 4 Ci, thereby increasing yields of research radiotracers. While the JSW can only irradiate one target at a time, the IBA is capable of irradiating two targets simultaneously and has been the main workhorse cyclotron. In addition to 18FF- production, this cyclotron is also used for 18FF2 bombardment for electrophilic radiosyntheses. Despite its older design and lower yields, the JSW has an advantage of a higher particle energy and capability to produce alpha particles; this is a rare and valuable asset and enables our facility to produce novel radionuclides for biomedical research. In particular, the JSW currently is used to produce At-211, a radionuclide that has potential in targeted systemic radiotherapy.
The facility is divided into two sections: a clinical production laboratory where the radiopharmaceuticals used in routine diagnostic scans and clinical studies are produced, and a multiuse research area in which new radiotracers are developed for cell studies, animal studies and other research uses."
"The clinical production laboratory is operated under cGMP regulations.
The DNA Sequencing Facility provides reliable, long read, automated Sanger sequencing with fast turnaround; microsatellite-based genotyping and fragment analysis; plasmid and BAC DNA preparation and purification; and related molecular biological services including PCR, cloning, sub-cloning, site-directed mutagenesis, and preparation of targeting vectors for gene targeting in mice. It also provides services and support for analysis and interpretation of sequence data as well as the design of approaches to complex sequencing projects.
For the last four years the facility has been providing Roche 454 sequencing service that includes library preparation, emulsion PCR and pyrosequencing for both genomic DNA and amplicons. Data analysis is provided in each project depending on the investigator’s specific need.
Ion Torrent's Personal genome machine (PGM) is the latest addition at the facility. Known for scalability, simplicity and speed, this inexpensive technology is advancing fast to achieve new goals in terms of throughput and read length. The maximum read length and the throughput available at this point is 200 b and 1 Gb respectively. The applications are similar to those of long-read 454 sequencer and includes targeted resequencing of barcoded samples, sequencing of captured library, sequencing of bacterial and viral genomes, sequencing of metagenomic samples, RNA-seq specially small RNA sequencing and validation of sequence data obtained on other platforms. The sequencer comes with Torrent Suite, the Torrent server analysis pipeline that is the primary software used to process raw data acquired by PGM sequencer to produce sequence read files. The base calls are in both SFF and FASTQ file formats for easy downstream analysis with third party analysis tools. The Torrent suite performs filtering, trimming, mapping with the generation of a Variant Caller report. This long read sequencer is going to bring down the cost of new generation sequencing significantly.
The range of services mentioned above along with the expertise of the facility personnel enables this core to provide full support for investigators at Penn, who can easily obtain fast, reliable data on genes of interest, whether they are doing targeted or whole genome tumor genome sequencing, deep resequencing, screening clones for sequences of interest, establishing the identity of new clones, or searching for mutations in specific genes.
Effector and memory lymphocytes, unlike naïve lymphocytes, can efficiently enter extralymphoid tissues as well as sites of inflammation and infection. Subsequently, lymphocytes enter the afferent lymph to reach draining lymph nodes. After a short time period of residency, lymphocytes exit the lymph node via the efferent lymph, which brings them back into the blood. This dynamic process of lymphocyte recirculation, which is tightly regulated at each step, is essential for immune surveillance and defense against pathogens, but it can also contribute to the development of inflammatory diseases.
My laboratory seeks to understand the regulation of lymphocyte recirculation as well as the microenvironmental localization of effector and memory lymphocytes within extralymphoid tissues, especially the skin. Currently, we are interested in defining the molecules involved in lymphocyte exit from extralymphoid tissues and the significance of this process to both protective and pathologic tissue immune responses. Another main interest of the lab is to determine the lymphocyte subsets involved in organ-specific immunity, with a focus on mobile surveillance mechanisms.
My lab uses a unique comparative immunology approach. We complement in vivo mouse models with a classic model of lymph cannulation in sheep that allows us to analyze lymphatic compartments that are inaccessible in rodents or humans. We also analyze human specimens to address whether our findings in ovine and mouse systems are relevant to human health. Finally, we are also committed to advancing general knowledge of the ruminant immune system, as domesticated ruminants are of worldwide importance.
Understanding the mechanisms involved in lymphocyte trafficking and recirculation through different organs not only reveals important components in the pathogenesis of inflammatory and infectious diseases, it also provides tools to therapeutically manipulate protective and pathogenic immune responses.
The Department of Pharmacology at Penn is one of the oldest and most distinguished in the country, and we are at the forefront of the discipline in the new millennium. We rank first for NIH funding amongst such Departments. Our science uses the tools of molecular and cellular biology, analytical and structural biology and mechanism based clinical investigation to discover and elucidate the action of novel therapeutics. The traditional strength of the Department has been in neuropharmacology. However, in the past decade we have expanded this considerably and have established robust programs in cardiovascular pharmacology and cancer pharmacology. Genomics and proteomics are becoming increasingly important tools throughout the Department. These interests have attracted a large number of faculty with expertise in cell signaling, spectroscopy and models of human disease. The Proteomics Cores of both the Penn Genomics Institute and ITMAT are led by Ian Blair, Vice Chair of the Department, and housed adjacent to Departmental space.
The Penn Diabetes Research Center (DRC) participates in the nationwide inter-disciplinary program established over thirty-five years ago by the NIDDK to foster research and training in the areas of diabetes and related endocrine and metabolic disorders. The Penn DRC is located in the newly opened Translational Research Center, which is a component part of a single integrated building providing health services for patients, biomedical research laboratories, and education space. The Penn DRC serves over 110 diabetes-oriented investigators primarily from the Perelman School of Medicine, but also from other Schools within the University of Pennsylvania as well as additional Philadelphia institutions including Jefferson and Temple.
The EGG (Early Growth Genetics) Consortium represents a collaborative effort to combine data from multiple genome-wide association studies (GWAS) in order to identify additional human genome loci that have an impact on a variety of traits related to early growth.
The consortium has initially studied child birth weight (Freathy et al. Nature Genetics 2010, Horikoshi et al. Nature Genetics 2013), as well as performing meta-analyses of more detailed measures of birth head circumference (Taal et al. Nature Genetics 2012, Ikram et al. Nature Genetics 2012), birth length (van der Valk et al. Human Molecular Genetics 2014), childhood obesity (Bradfield et al. Nature Genetics 2012), pubertal growth (Cousminer et al. Hum Molec Genet. 2013), Tanner stage (Cousminer et al. Hum Molec Genet. 2014) and childhood BMI (Felix et al. Hum Molec Genet. 2015). Through these efforts, many loci influencing these traits have been identified, a subset of which also influence adult traits and diseases.
The EMRL is a full service, shared resource facility at the University of Pennsylvania’s School of Medicine. The EMRL primarily serves the biomedical research community at the University of Pennsylvania but offers high quality EM imaging services to researchers beyond Philadelphia and academia. Our staff of experienced professionals performs routine TEM, SEM, single particle and tomographic image reconstructions, and image analysis of all types of biological material. The facility is well equipped with 3 TEMS: a JEOL1010 with a 1K x 1K video rate AMT digital camera, a FEI Tecnai12 120KeV S/TEM microscope which is equipped with a 2K x 2K Gatan 894 camera and EDAX electron dispersive SiLi detector, and a FEI TF20 200 KeV S/TEM microscope with the latest generation CMOS direct electron detector, 2K x 2K video rate Gatan Orius camera as well as a Fischione HAADF for STEM Z imaging. The facility also houses a FEI Quata250 environmental SEM.
The Epstein Laboratory studies cardiovascular development, the genetics of congenital heart disease and cardiovascular regenerative and stem cell biology. The lab has a long-standing interest in congenital heart defects involving the outflow tract of the heart, the role of neural crest, the epicardium and the second heart field. More recent areas of focus include the cardiac inflow tract and the pulmonary veins and the origin of anomalous pulmonary venous return.
Other areas of interest include the factors and genes involved in progressive lineage restriction of cardiac progenitor cells and the role of epigenetics in progenitor cell expansion and differentiation. The lab is also interested in the implications of these studies for the development of new therapies for adult cardiovascular disorders including heart failure and arrhythmia. Specific projects have focused on the role of Notch and Wnt in cardiac progenitors, semaphorin signaling in the developing vasculature, the function of a novel homeobox gene Hopx and histone deacetylases in stem cells and the heart, and the role of the type I Neurofibromatosis gene (Nf1) in mouse and zebrafish cardiac development.
Our lab is part of the Department of Cancer Biology and the Abramson Family Cancer Research Institute, two outstanding collectives of scientists working on diverse cancer related problems. Our work is dedicated to deconstructing the multistep process of tumorigenesis with the ultimate goal of developing potent strategies to eliminate cancer.
Our laboratory has two areas of interest – prostanoid biology and the role of peripheral molecular clocks in cardiovascular biology, metabolism and aging. Perhaps the distinguishing feature of our groups is that we pursue interdisciplinary translational science with a focus on therapeutics. Thus, we work in different model systems – mammalian cells, worms, fish and mice – but also in humans. Ideally we develop quantitative approaches that can be projected from our experiments in the model systems to guide elucidation of drug action in humans. To this end, we have long utilized mass spectrometry, initially to target the arachidonate derived lipidome, but more latterly also the proteome.
Currently, we are interested in several aspects of prostanoid research. We utilize a remarkably broad array of mutant mice to elucidate the biology of the two COX enzymes and the prostanoid receptors. We are particularly interested in the comparative efficacy and safety of pharmacological inhibition of COXs versus the microsomal PGE synthase– 1. We are interested in the potentially countervailing actions of prostanoids on stem cell differentiation and in elucidating the broader cardiovascular biology of prostaglandins D2 and F2α. Finally, besides inhibitors of mPGES–1 we are interested in the translational therapeutics of various receptor antagonists, aspirin and fish oils.
In the area of clock biology, we are probing the role of the clock in aging in mice and worms and using cell specific deletions of core clock components to look at how communication paradigms between discrete peripheral clocks influence cardiovascular biology and metabolism. Finally, we are taking systems approaches to investigate how perturbation of peripheral clocks result in central clock dependent phenotypes.
Finally, we are involved in the interdisciplinary PENTACON consortium designed to integrate basic and clinical research in 5 systems – yeast, mammalian cells, fish, mice and humans ( both in detail and at scale) – with the objective of predicting NSAID efficacy and cardiovascular hazard in patients.
The Flow Cytometry Core Laboratory provides access to state of the art instrumentation and professional flow cytometry services to members of the research community of The Children's Hospital of Philadelphia and University of Pennsylvania; investigators from outside the campus are welcome to our facility. The lab has space on the 12th floor of the Leonard and Madlyn Abramson Pediatric Research Center and on the fourth floor in Colket Translational Research Center. The staff has the required expertise for performing a variety of flow cytometry applications, including but not limited to sample processing for surface and intracellular staining, functional assays, complex multi-color flow cytometry analyses and cell sorting.
The Wistar Institute Flow Cytometry Shared Resource provides flow cytometric services, training, advice, and support for the use of flow cytometric techniques by Wistar Cancer Center investigators, as well as the greater basic research community.
The Flow Cytometry and Cell Sorting Resource Laboratory is currently recognized as one of the largest and most comprehensive flow cytometry laboratories in the US. In 2010 it was designated a laboratory of exceptional merit by the National Cancer Institute. Using state-of-the-art technology, the resource provides a broad array of, instrumentation, support, education and consultation to the research community at the University of Pennsylvania. A wide variety of cell sorting applications are supported, from high-speed multicolor (up to 14 colors) cell sorting to low-speed, large nozzle, improved viability sorting. Additionally, a wide variety of cell analysis services (up to 20 parameters) are offered, from traditional analog, easier to use tabletop analyzers to many-laser, many-color, high-speed, fully-digital modern instrumentation. Currently the facility offers 6 cell sorters and 19 analytical instruments. A very active training and consultation program is in place to support these activities. The Scientific Director, Dr. Jonni Moore, and the Technical Director, each have over 25 years experience in the field of cytomics. Researchers at the University of Pennsylvania are increasingly engaged in research projects that require 8-plus-parameter cell sorting of infectious cells and primary human tissues. Investigators using the Flow Cytometry and Cell Sorting Shared Resource have access to virtually any type of cytometric services required for a vast array of applications.
GEFOS stands for the GEnetic Factors for OSteoporosis Consortium. It is a large international collaboration involving various prominent research groups.
Osteoporosis is a common age-related complex disease with a strong genetic component. Osteoporotic fractures account for considerable disease burden and costs. The genes responsible, however, are poorly defined. It is by now generally assumed that - like for many other complex diseases such as diabetes and cardiovascular disease - many gene variants are responsible but each with subtle effect. In a previous EU FP5 funded project, named GENOMOS, we have improved on this situation by bringing together several of Europe's largest collections of osteoporosic study populations with DNA available, and analysing the most commonly studied.
With the GEFOS project we here propose to capitalize on the success of GENOMOS by using the most advanced gene discovery tools that have become recently available, i.e., Genome Wide Association (GWA) analysis with high density SNP arrays, to identify common risk gene variants for osteoporosis.
The Penn Physical Medicine and Rehabilitation Gait and Biomechanics Laboratory focuses on motion and gait analysis for both patient care and research in order to better diagnose, treat, and understand movement and gait disorders.
Gait analysis is covered by insurance to aid in surgical planning in patients with gait disorders associated with cerebral palsy. Gait analysis can still be used for other applications but will be charged as fee for service
We are studying a mutant gene which when homozygous leads to a lethal kidney disease in mice. These mice undergo a spontaneous autoimmune reaction which involves multiple immune pathways. We have cloned the relevant gene, and have found that it codes for a mitochondrial protein similar to trans-prenyltransferase. This enzyme is needed for isoprenylation of coenzyme Q (CoQ), and is now known as prenyl diphosphate synthase subunit 2 (Pdss2). The mutant mice have defective mitochondria, as demonstrated by ultrastructural analysis, and we believe that this defect leads to the death of glomerular podocytes. This in turn leads to an autoimmune response which involves both the tubular interstitium and the glomeruli. The kidney disease can be prevented to some extent by CoQ supplementation, and to an even greater extent by probucol. The mechanism by which probucol does this has not been fully elucidated, but we and our collaborators (Dr. Marni Falk at CHOP and Dr. Cathy Clarke at UCLA) have demonstrated that it increases the endogenous production of CoQ.
In collaboration with Dr. Julie Blendy, Dr. Harry Ischiropoulos, and their students, we have demonstrated that these mutant mice also have neuromuscular defects that resemble Parkinson’s disease. We are currently working on several possible therapies which have the potential of treating these problems.
The human disease with the greatest similarity to this phenotype is focal segmental glomerular sclerosis, or FSGS. It is well known that there is a significant genetic component to FSGS susceptibility, and in collaboration with a group at the NIH, we have obtained evidence that PDSS2 is one of the genes that is involved in this susceptibility.
The Genetic Diagnostic Laboratory is a non–profit laboratory at the University of Pennsylvania. Established in 1994, the Genetic Diagnostic Laboratory has had the pleasure to serve patients, physicians, and other members of the medical and research community in many states in the U.S., as well as in over 24 countries worldwide.
Our mission is to evaluate an individual's DNA to discover a genetic cause for their disease or physical symptoms, provide interpretation of the genetic finding and its association with disease, develop new methods for analyzing genes, and introduce new testing to improve patient care.
The Genetic Diagnostic Laboratory is CLIA certified and has state permits for California and Maryland. The staff of the Genetic Diagnostic Laboratory includes highly trained and experienced laboratory technicians, as well as a genetic counselor, who work continually to provide their services in a timely and professional manner.
The Genetic Investigation of ANthropometric Traits (GIANT) consortium is an international collaboration that seeks to identify genetic loci that modulate human body size and shape, including height and measures of obesity. The GIANT consortium is a collaboration between investigators from many different groups, institutions, countries, and studies, and the results represent their combined efforts. The primary approach has been meta-analysis of genome-wide association data and other large-scale genetic data sets. Anthropometric traits that have been studied by GIANT include body mass index (BMI), height, and traits related to waist circumference (such as waist-hip ratio adjusted for BMI, or WHRadjBMI). Thus far, the GIANT consortium has identified common genetic variants at hundreds of loci that are associated with anthropometric traits.
The Genetics of Personality Consortium (GPC) is a large collaboration of genome-wide association studies for personality. The aim of the GPC is to detect genetic variants associated with personality traits, and to further our understanding of the molecular genetic basis of personality traits.
The Wistar Genomics Facility serves as a hub for consultation and scientific interactions relating to nucleic-acid based methods and provides expertise and support to insure the best possible use of emerging nucleic-acid technologies.
In addition to consultation and collaboration with Wistar Cancer Center members, the Facility provides services to the greater scientific community.
The establishment of this facility was supported in part by an NCI Cancer Center Support Grant and equipment grants from the Commonwealth of Pennsylvania, The Pew Charitable Trusts and the National Cancer Institute.
The aim of this consortium is to study the genetic determinants of blood low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides.
The Healthcare Analytics Unit (HAU), a core facility of CHOP’s Research Institute that is co-directed by CPCE and PolicyLab, administers these resources. HAU’s staff has expertise in managing and using various data sources, ranging from electronic health records and clinical trial or registry data to administrative, claims, or survey data.
The HAU serves as a resource for CPCE, PolicyLab, and other CHOP investigators using complex data to address research questions. HAU provides services in data extraction and management, statistical programming, biostatistics analysis, and analytics data consultation.
The Children's Hospital of Philadelphia and the Beijing Genomics Institute (BGI) have formed a collaborative genome center entitled BGI@CHOP. Together, these elements form The High-throughput Sequencing (HTS) Core with increased capacity, expertise and analytical resources for conducting next-generation sequencing studies. The HTS Core will provide automated library construction and high-quality, high-throughput sequencing services for whole genome and whole exome samples.
The High-throughput Screening (HTS) core provides the Perelman School of Medicine community with professional HTS screening services to identify genes or organic small molecule modulators of signaling pathways, cellular phenotypes, and protein function in models of human disease. Core staff will educate and assist scientists with HTS assay development, optimization, miniaturization, and validation; maintain libraries of siRNA, shRNA, cDNA, and FDA approved/FDA-like organic small molecule libraries for HTS; and provide robotics infrastructure and technically trained staff for HTS, including small screens of user defined libraries. The High-throughput Screening core also provides direct assistance with preparation of grant applications by drafting experimental designs approaches and providing Letters of Support, offering HTS resources and analysis expertise for the proposed research.
The PennHPC facility opened in April of 2013 to meet the increasing growth in genomics processing and storage, as well as growth in other scientific areas requiring computational capacity such as imaging and biostatistics/bioinformatics. The cluster is managed by two fulltime system administrators, and is located at the Philadelphia Technology Park, a Tier-3, SSAE 16/SAS 70 Type II Audit compliant colocation/datacenter facility.
The Histology and Cellular Localization Core provides training and research support in microscopy, anatomy and histology of chemosensory systems. Core personnel work with Monell researchers to develop and optimize in-house procedures and to establish cutting-edge techniques in histology and cell anatomy. The Core provides centralized services such as tissue sectioning and in situ probe preparation. The Core facility is equipped with cryostats, fluorescence microscopes, confocal microscopes, and a two-photon microscope.
The Histology and Gene Expression Core Facility provides expert professional services for members of the Cardiovascular Institute. Services for non- Institute investigators are available on a fee-for-service basis as time permits. The Histology and Gene Expression Core offers all histology-related services include tissue processing, embedding, sectioning, staining, immunocytochemistry and InSitu Hybridization.
This facility provides basic histology services. These include fixing, processing and paraffin embedding of all types of tissues for light microscopy (i.e. routine stains, immunohistochemistry or in situ hybridization). Routine hematoxylin and eosin staining as well as special staining is done in the lab. Slides are prepared for immunohistochemistry and in situ and immunohistochemistry.
Frozen sectioning is also available. It is advisable to contact the facility about freezing techniques so the best sections can be obtained.
Our laboratory studies the mammalian circadian clock using genomic and computational tools. We use these tools to discover new clock genes, learn how the clock keeps time, and how it coordinates rhythms in physiology and behavior. This clock research drives development of genomic and computational methods that we apply to other areas of biology. Finally, we recognize biological complexity and conduct this research at the network, rather than single gene, level.
The Human Immunology Core provides reagents and scientific expertise to investigators studying immune function in humans. The core serves as a central facility for cell and tissue processing, generation of human blood cell products, and the performance of qualified cellular and molecular immune assays for early-phase clinical trials. Assays include multicolor immunophenotyping, high throughput sequencing of T cell receptor and B cell receptor genes, luminex, ELISPOTs, ELISA and expert scientific and technical consultations to investigators wishing to develop or incorporate the newest immunology technologies into their research.
Dr. Hunter has been working on various aspects of basic parasitology since 1984 and for the last 25 years there has been a focus on understanding how the protective immune response to Toxoplasma gondii develops and how this relates to other parasitic infections.
The Hunter Laboratory team has focused on the innate events that lead to the development of long term protective immunity mediated by T and B cells. These studies led us to develop expertise in cytokine biology and, while the focus has been in understanding their role in infectious disease, these findings are frequently relevant to cytokine function in autoimmunity and inflammatory processes associated with human disease.
For example, as part of studies to understand how IL-12 family members affect immunity to the T. gondii, we showed that IL-27 was important in limiting the T cell-mediated infection-induced inflammation. We have defined the mechanisms used by IL-27 to influence the immune system and our work has been shown to be relevant to inflammatory processes in multiple experimental systems that includes other infections as well as models of auto-immune inflammation, asthma and cancer.
Since toxoplasma causes a chronic infection in the brain there has been a long-term interest in the neuropathogenesis of infectious diseases and how lymphocytes access and operate in this immune privileged site.
In this laboratory we have developed all of the skills required for the routine analysis of multiple innate immune parameters and to quantify DC, macrophage, NK, T and B cell responses to infection.
We are also able to utilize different combinations of transgenic parasites (replication deficient, expressing fluorescent reporters, distinct model antigens OVA and E and the Cre recombinase) and TCR transgenic T cells to provide higher resolution analysis of individual parasite specific CD4 and CD8 T cell populations and apply multi-photon microscopy to image the innate and adaptive response to T. gondii.
Asthma is a chronic inflammatory disease, which is associated with the recruitment of mast cells to the lung and their activation. It is well known that aggregation of high affinity IgE receptors (FceRI) on mast cells and the subsequent mediator release contributes to the development of allergic asthma. However, emerging evidence suggests that transactivation of G protein coupled receptors (GPCRs) for the complement component C3a contributes to the exacerbation of allergic diseases. The main focus of our laboratory has been to delineate how G protein coupled receptor kinases (GRKs) and the adaptor molecule β-arrestin regulate C3a receptor function in mast cells. We unexpectedly found that GRK2 and β-arrestin2 serve as novel adaptor proteins to promote IgE-mediated mast cell chemotaxis, degranulation and cytokine gene expression. We are currently utilizing both in vitro and in vivo approaches to delineate how GRK2 and β-arrestin2 regulate FceRI signaling in mast cells to modulate allergic asthma.
Surface epithelial cells, when activated by pathogen-associated molecular patterns (PAMPs) release small cationic antibacterial peptides (AMPs), known as defensins and cathelicidins. These AMPs display potent antimicrobial activity, modulate immune responses and likely participate in the exacerbation of allergic diseases such as asthma and urticaria. Recently, we made the unexpected observation that AMPs activate human mast cells via a novel GPCR (Mas-related gene X2; MrgX2). Most interestingly, we found that unlike C3a receptor, MrgX2 is resistant to regulation by GRK2 or β-arrestin-2. It is noteworthy that unlike human mast cells, murine mast cells do not express MrgX2 and are resistant to activation by AMPs. We are currently engrafting human CD34+ hematopoietic stem cells (HSCs) into severely immune-deficient mice. In addition to human immune system, these “HUMANIZED MICE” develop human tissue mast cells are responsive to AMPs for activation in vivo. We are currently using the humanized mouse model to determine the role of MrgX2 and its signaling on anaphylaxis and asthma in vivo.
The ITMAT Bioinformatics Facility provide project based bioinformatics support for ITMAT translational researchers. Our focus has been on providing the computational infrastructure and programming support needed to conduct high-throughput proteomics experiments. We also support other genomics high-throughput technologies to a lesser extent. See the resources page for more information on our projects and what we have to offer.
The projects range from building easy to use Web applications for data analysis pipelines, one-off scripting, clinical and basic science research support, algorithm development. Recent efforts have focused on explorations of new models of computation, specifically Cloud Computing and GPUs, for use in genomic scale research. Feel free to contact us for more information.
The Imaging Facility is a shared resource with the primary goal of providing exceptional microscopy and imaging services, as well as individual access to a variety of state-of-the-art imaging resources for members of the Wistar research community. The imaging systems have been designed to be extremely flexible to reflect a broad range of challenging scientific questions and specimens. Each system provides a combination of illumination, optics and image capture options. Diverse subjects ranging from fluorescently tagged live cell cultures and stained tissue sections, to 3D tumor spheroids and low magnification explanted tissues, can be accommodated with available systems.
Current equipment includes standard upright and inverted fluorescence microscopes, a customized live-cell time lapse microscope capable of 6D imaging, a laser scanning confocal microscope, a 2-photon microscope designed for in vivo imaging, a small animal, whole body luminescence and fluorescence imager, special low magnification (photomacrography) systems as well as a variety of traditional photographic cameras, lenses and lighting equipment. Users of the facility may be trained for unassisted use of all core assets, or they may elect assisted service with the facility staff performing the imaging.
The Imaging staff also provides assistance to researchers with additional aspects of their imaging requirements. Ideal approaches to specimen documentation are often unique to the experiment and the staff can help design the most effective imaging protocols to answer a particular question. On-site assistance is available to help investigators get the most out of their own systems. Image analysis and specialized Photoshop training, creative imaging for journal covers, and guidance on digital imaging ethics help to round out the services available from the facility.
Immune responses to products of viral vectors have posed formidable barriers to efficient gene therapies. The important immune effectors of the immune response include CD4+ T helper cells, CD8+ cytotoxic T cells, which are responsible for mediating elimination of transgene expression and B cells which produce neutralizing antibodies that block effective readministration of vector. In addition immune responses directed to neoantigens expressed by the transgene in vector-transduced cells, are also responsible for the rapid elimination of transgene expression. The Immunology Group is responsible for performing various assays to evaluate both cell mediated- as well as humoral immune responses in animal models of gene therapies. In this respect, the Group has undertaken analyses of immune responses in pre-clinical trials in gene therapy in mice, rats, rhesus monkeys, and dogs and in several clinical trials. These assays monitor adenovirus-, adeno-associated virus- and transgene-induced cell mediated and humoral immune responses.
The following schematic illustrates the various immunological processes for which the Immunology Group has developed methodologies:
Figure Legend: Antigen taken by antigen presenting cells (APC) is processed and presented by MHC class I to CD8 T cells , and MHC class II to CD4 T cells . Recognition of the antigen, along with costimulatory molecules (B7-CD28; CD40-CD40 ligand) results in activation of antigen-specific CD4 T cells, which leads to lymphoproliferation and cytokine secretion . Depending on several conditions (e.g. strength of antigen signaling, costimulation, cytokines secreted by APC, etc.) CD4 T cells differentiate into either TH1 or TH2 type cells. TH1 cells secrete predominantly IFNg (interferon-gamma), which plays a role in activation of cell mediated immune responses which culminates in activation of cytotoxic T lymphocytes . CTL have been shown to be responsible for elimination of transduced cells in vivo by effector mechanisms involving Fas-FasL and perforin-granzymes. TH2 cells on the other hand secrete IL-4, which helps B cells differentiate into antibody secreting plasma cells. Secretion of neutralizing antibodies results in blocking of vector readministration. The nature of the neutralizing antibody response can be measured by determining the antigen (by Western blot) and isotype of the immunoglobulin.
Understanding the molecular mechanisms involved in the cascade of events from antigen uptake by antigen presenting cells to differentiation of T and B cells, will allow development of therapeutic immunosuppressive agents to allow persistent transgene expression and ability to readminister viral vectors.
The Penn Institute for Regenerative Medicine (IRM), which has been at the forefront of stem cell research and translational medicine, established the iPSC Core in 2009 to promote this powerful technology on campus and surrounding institutions. The goals of the Core are:
• to facilitate derivation of induced pluripotent stem (iPS) cells from somatic cells;
• to provide expertise and training to researchers in embryonic stem (ES)/iPS cell culture;
• and to serve as a resource for sharing iPS cell lines and iPSC technology within the UPenn and the broader scientific community.
The primary role of the IBI is to provide an interdisciplinary home for basic science faculty in biomedical informatics, as well as mechanisms to connect genetic, genomic, and phenotypic data and knowledge to provide personalized medicine to Penn Medicine patients. These research communities will be encouraged to collaborate through partnerships with clinical and basic science departments and centers, IBI pilot grant programs, core services, co-mentoring trainees, seminars and colloquia, and through yearly retreats.
Established in 2007, Penn’s Institute for Regenerative Medicine (IRM) was formed to promote basic discoveries in stem cell biology and regeneration, and to translate those discoveries into new therapies that may alleviate suffering and disease. Researchers at the IRM seek an understanding of how cells and tissues are formed as well as how they can be repaired or replaced when damaged or lost due to injury, disease or aging. This field of medicine is called regenerative medicine.
The Institute for Translational Medicine and Therapeutics (ITMAT) supports research at the interface of basic and clinical research focusing on developing new and safer medicines. ITMAT includes faculty, basic research space, and the Clinical and Translational Research Center (CTRC), which now includes the former General Clinical Research Center (GCRC) of both Penn and the Children's Hospital of Philadelphia (CHOP). ITMAT also offers research cores, educational programs (including a Masters in Translational Research), and research centers.
The ICBP consortium is an international effort to investigate blood-pressure genetics. The consortium was formed by two parent consortia, the CHARGE-BP consortium (Cohorts for Heart and Aging Research in Genomic Epidemiology - blood pressure) and the GBPGEN consortium (Global Blood Pressure Genetics Consortium).
The International Genomics of Alzheimer's Project (IGAP) is releasing the summary results data from the 2013 meta-analysis of Genome-wide Association (GWA) data in Alzheimer's disease, in order to enable other researchers to examine particular variants or loci for their evidence of association. The files include p-values and direction of effect at over 7 million directly genotyped or imputed single nucleotide polymorphisms (SNPs). To prevent the possibility of identification of individuals from these summary results, allele frequency data are not released.
International Headache Genetics Consortium (IHGC) is a multinational research collaboration studying genetic causes and background of headache and related disorders. It aims to boost research in this area by bringing together the increasing wealth of well-characterised genetic information and high quality diagnostic data, as well as analysis expertise, to discover basis for future treatments.
Consortium members include migraine research groups from Australia, Denmark, Estonia, Finland, Germany, Iceland, the Netherlands, Norway, Spain, Sweden, the UK and USA.
In recent years the IIBDGC has focused on collecting very large datasets from a diverse set of countries via world-wide collaboration. In addition to enabling the discovery of all these genes, we also try to dig a little deeper into what these associations actually mean. Our latest paper takes this further than we ever have before, involving analysts from a dozen research groups and using the latest statistical techniques to look for patterns across the 163 regions.
The combination of all this information allowed us make new statements about IBD risk that no single locus can tell us: IBD is not just genetically similar to other diseases of immunity, but is particularly closely related to certain inflammatory disease such as psoriasis. IBD risk is not only related to changes in the immune system, it is related to a particular subset of immune cells and signals. Not only is IBD risk related to susceptibility to bacterial infection, it is remarkably strongly connected with susceptibility to the family of bacteria that includes leprosy and TB.
In contrast to just five years ago, discovering genes for disease is no longer the hard part. Future studies, including those of the IIBDGC, will have to focus not just on discovering new associations, but also on turning those associations into new biological understanding.
In the Interventional Radiology Catheter Lab minimally invasive procedures are performed via fluoroscopy, ultrasound and endoscopy. Percutaneous vein and arterial access is performed via ultrasound-guided technique. Surgeons are then able to guide catheters, ballon dilation, and other small instrumentation through the blood vessels. Procedures that have been performed in the lab are:
• Aneurysm creation
• Balloon angioplasty
• Embolization (coil, glue, embospheres)
• Inferior vena Cava (IVC) filter placement & retrieval
• Selective arterial catheterization
• Stent placement (renal, gastric, iliac)
• Peroral gastroenteric anastomosis
This lab has capabilities for full surgical and anesthesia protocols and full fluoroscopy imaging. Included in the lab are a small office space, an LCD monitor and computer for the fluoroscopy unit, eye wash station and a surgeon scrub sink.
The Investigational Drug Service (IDS) is the research pharmacy for the University of Pennsylvania, providing services for clinical and pre-clinical drug and device trials to investigators at all Penn schools, UP Health System hospitals and clinics and affiliated institutions.
The IDS is able to offer a range of services to investigators, from preparation, dispensing and inventory management for inpatient and outpatient trials, to formulation of blinded dosage forms or placebos to match existing medications, randomization tables and blinding schemes, specialized packaging and distribution, as well as limited release testing of finished products. We can assemble draft materials for CMC (IND) submissions or draft language for protocols, describing our activities related to your specific protocol. As a core facility, we pass along our actual costs on an hourly basis for these services. We maintain a highly secure, temperature-controlled facility and an electronic inventory system.
General Mission Statement:
To serve as a resource for Center Investigators that are studying pancreatic islet cell biology by offering islet isolation and culture, functional phenotyping of islets and providing consultation and help to develop strategies how to use the services of the core optimally or attempt to modify available technologies to solve particular problems.
Please remember to acknowledge the Institute for Diabetes, Obesity and Cardiovascular Metabolism, the DRC grant (P30DK19525) and the services of the Islet Cell Biology Core in any ensuing research publications.
Description of Research
Barrett’s Esophagus Focus:
Esophageal adenocarcinoma (EAC) has been the fastest rising malignancy in the U.S.. Several conditions increase the risk for the development of EAC, including obesity, smoking, diet, acid reflux, and, most significantly, Barrett's esophagus (BE). BE occurs at the gastroesophageal (GE) junction and is the replacement of normal squamous esophageal mucosa with an intestinalized columnar epithelium. It typically arises in response to chronic acid exposure and is associated with acid reflux. Importantly, the histologic precursor lesions and molecular mechanisms underpinning BE pathogenesis remain poorly understood. One reason is the paucity of experimental models for BE. Our research has focused on this problem, and the development of innovative, genetically based and physiologically relevant human cell culture and transgenic mouse models for BE is an important objective of my lab. We are broadly pursuing several strategies including exploring the role of intestine-specific transcription factors like Cdx1, Cdx2, and Hath1, as well contributions by proinflammatory cytokines (IL-1beta), eicosanoids (Cox-2), and autophagy in BE pathogenesis and progression to neoplasia.
Intestinal Stem Cell Focus:
Stem cells are defined by the capacity for long-term self-renewal and multilineage differentiation. Until relatively recently, our understanding of stem cell biology, as well as their role in many human disease processes from aging to cancer, has been rather limited. Moreover, interest in harnessing the stem cell’s capacity for self-renewal to promote organ and tissue regeneration cuts across many medical disciplines. Recently, genetic studies have identified several robust markers for stem cell populations in the intestine. These advances now make it possible to isolate stem cell populations for more advanced molecular investigations. One important challenge encountered by stem cells is to correctly determine their tissue identity based on environmental cues. Errors in stem cell identity are encountered in intestinal metaplasia of the esophagus and stomach, as well as many gastrointestinal cancers. We are exploring these questions using novel transgenic mouse models of gastric intestinal metaplasia and in mice with alterations in the intestinal stem cell niche.
More recently we have begin using live cell confocal microscopy to investigate how the intestinal stem cell niche is established, the relationship between niche and stem cells, how intestinal crypts fission, how stem cells undergo mitosis, and early events in neoplastic transformation.
T cells integrate multiple signals from their environment. The culmination of these signals direct the fate of developing thymocytes, dictating the outcome of thymocyte selection and T-regulatory (Treg) cell development. Mature peripheral T cells also integrate multiple signaling pathways during encounter with pathogens and are directed to differentiate into one of several T cell effector subsets.
We are interested in understanding how specific pathways direct these differentiation steps in thymocytes and peripheral T cells. Currently we are focusing on signaling pathways and epigenetic modifiers that have recently been implicated in T cell lymphomagenesis with an aim towards understanding how these pathways and enzymes direct both normal and malignant T cell biology. Some active areas of investigation include the following:
• T cell activation leads to transient changes in the activation states of many proteins and enzymes, but it also results in heritable changes at the epigenetic level. DNA methylation is a common epigenetic modification that is regulated via both active and passive mechanisms. TET2 is a methylcytosine dioxgenase involved in the active demethylation of DNA and is frequently mutated in a specific class of T cell lymphomas. Our lab has shown that TET2 regulates the development of memory CD8+ T cells as well as CD4+ T cell differentiation. We are currently identifying the targets of TET2 to understand the mechanism by which it regulates T cell differentiation. We are also interested in CXXC5, a negative regulator of TET2, to determine its TET2 –dependent and –independent functions in T cell activation and differentiation.
• The GTPase RhoA is important for thymocyte development and is activated downstream of the T cell receptor and integrins. RhoA regulates actin reorganization and has been implicated in T cell metabolism. Recently, RhoA mutations have been identified in T cell lymphomas, often co-occurring with TET2 loss-of-function mutations. Using both in vitro and in vivo models of regulated RhoA expression, we are investigating the mechanism of RhoA function in healthy and diseased states.
The Kaestner lab is employing modern mouse genetic approaches, such as gene targeting, tissue-specific and inducible gene ablation, to understand the molecular mechanisms of organogenesis and physiology of the liver, pancreas and gastrointestinal tract.
1) Regulation of T cell responses
T cells are pivotal players in the immune response. They are beneficial in combating infections and cancer but can also be harmful in autoimmunity and immunopathologic states. T cell activation is primarily initiated by intracellular signals emanating through their T cell receptor. These signals can be further modified by engagement of other cell surface receptors and by negative regulators of signaling. Currently, we study the role of the NK cell receptor NKG2D in controlling T cell activation. In addition, we are investigating the roles of negative regulators of calcium and daicylglycerol signaling in T cell activation and differentiation.
2) Regulatory T cell expansion and homeostasis
In addition to the cell-intrinsic regulation of T cell activation as described above, T cells are controlled cell extrinsically by regulatory T cells. Regulatory T cells represent a subset of CD4+ T cells that possess the ability to suppress the activation and expansion of other conventional CD4+ T cells. They are distinguished from conventional T cells by constitutive expression of CD25 and the transcription factor Foxp3. The importance of regulatory T cells is evidenced by the severe autoimmunity that develops in mice and humans lacking regulatory T cells. We are actively investigating how signal transduction processes affect the development, homeostasis, expansion, and function of regulatory T cells. We translate our findings to therapeutic approaches in the prevention of inflammatory diseases such as multiple sclerosis, graft-versus-host disease, diabetes, rheumatoid arthritis, and inflammatory bowel disease.
4) NK cell education and signaling
NK cells are innate immune cells that provide a critical line of defense against intracellular pathogens and tumors by displaying cytotoxicity and producing immune-activating cytokines. One key mechanism that regulates their activation involves the expression of activating receptors that are finely counterbalanced by inhibitory MHC class I-binding receptors. Thus, the interaction of NK cells with abnormal cells that have decreased MHC class I expression relieves the inhibition conferred by the MHC-binding inhibitory receptors, leading to activation and cytotoxicity by the NK cell. NK cells heterogeneously express one or more of the many inhibitory receptors, which are acquired by NK cells during later stages of their development. The heterogeneity of NK cell receptor expression allows NK cells to discriminate between cells expressing normal and abnormal amounts of various MHC class I molecules. As the signaling requirements of these receptors during development and effector function remain unclear, we have been investigating the signal transduction pathways during NK cell activation. In doing so, we have identified some key signaling molecules that are necessary for proper acquisition of MHC-binding inhibitory receptors during development. We are further investigating the molecular mechanisms that are responsible for regulating inhibitory receptor acquisition during NK cell development and how it relates to the functional outcome of the NK cell response.
A key property of living objects is that each object, whether they are proteins, cells, or whole organisms, has an associated generating process, that is, a decoding process whereby stored information is converted into a complex functioning biological object. For example, generating a protein involves translation and folding; generating an organism involves a cascade of gene regulatory and cell biological processes. We are interested in such bio-generative processes and understanding the temporal control and architectural constraints of these processes.
Questions include how to infer the organizational structure of such generative processes from available data, the evolution of control processes, and how the relationship between generative dynamics, variability, and the final form interact to determine the evolution of the biological object. Two central projects in our lab are using comparative transcriptome profiling of time-series to uncover the architecture of temporal control in yeast and using computational analysis of non-coding RNAs to understand the evolution of sub-cellular processes in neurons.
Since 2007, Jim Eberwine (Pharm) and I have been engaged in multiple joint projects concerning genomics of cell differentiation and cell diversity. Our labs collaborate in all kinds of projects where we bounce ideas off each other, design and carryout experiments together, and design analysis of data together. Many of the projects described below, especially in neuroscience are joint projects between our two labs.
In addition to these theoretical problems, we work on a wide range of collaborative projects and computational biology projects. Currently, these collaborations involve molecular control of neurons, functional prediction of sequence elements for genes involved in synaptic transmission, novel technologies for functional genomics, statistical analysis of whole-genome expression profiling, as well as software engineering bioinformatics analysis platforms. We employ a variety of techniques including discrete algorithms,simulations, statistical learning, dynamical systems and algebraic geometry, molecular biology, functional genomics, and single-cell genomics.
Our laboratory makes use of cell-free biochemical systems, model cell lines, and whole animals which have been genetically manipulated to probe various signal transduction pathways. Over the past several years we have become particularly interested in the regulation and integration of second messenger cascades by adapter molecules, those proteins which possess no intrinsic enzymatic properties, but which function by bridging protein-protein interactions.
Our laboratory is currently pursuing studies focused on mechanisms of B cell homeostasis and how these impact autoimmunity and aging. These have led to the characterization of a novel receptor for BLyS, a TNF family member that controls B cell numbers and determines the stringency of B cell selection.
Penn Dental Medicine houses a Radiance 2100 laser confocal microscope available for use by researchers throughout the School as well as others inside and outside the University.
Major histocomatibility complex (MHC) class II molecules are required for the normal development in the thymus of CD4+ T cells and function to present peptide antigens to those CD4 cells in the periphery.
The distribution of class II molecules is limited to thymic epithelial cells-where they are required for the positive and negative selection of CD4+ T cells-and in the periphery where they are required for the survival and activation of those T cells. We have developed a series of transgenic mice with restricted expression of the MHC class II molecule, I-Ab, and used them to investigate the requirement for different populations of antigen presenting cells in the thymic selection, peripheral activation, and tolerance of CD4+ T cells. Our most well studied model is the K14 mouse in which MHC molecules are restricted to thymic cortical epithelium-both thymic medullary epithelium and bone marrow-derived cells are class II negative. Positive selection of CD4+ T cells does occur in the K14 thymus; however, clonal deletion of autoreactive thymocytes can not be detected. Thus, K14 CD4 cells proliferate to I-Ab-positive APC in vitro and cause graft-versus-host disease when injected into MHC-identical hosts. Our current studies are directed toward understanding the peptide specificity, function, and pathologic potential of these autoreactive T cells:
1) Examination of a series of K14-derived autoreactive T hybridomas demonstrates that the autoreactive population of CD4 cells is polyclonal; however, we are beginning to identify the individual peptides responsible for stimulating the autoreactive response. To better understand the thymic selection processes in both K14 and wildtype thymi, we have also derived TCR transgenics from two of the hybrids and have begun to analyze the thymic development and peripheral function of autoreactive TCR transgenic CD4+ T cells in both K14 and wildtype mice of various haplotypes, including NOD, the diabetogenic genotype.
2) Development of autoimmunity: Adoptive transfer systems are being utilized to tease apart the T cell and target-organ abnormalities that must be present to initiate an autoimmune disease. Disease models include graft-versus-host disease, Herpes simplex keratitis, and Type I diabetes.
3) Requirement for MHC class II in other antigen presenting populations. Our newest transgenics utilize the mb-1 and CD11c promoters to reexpress class II molecules in the B cells and dendritic cells, respectively, of class II-deficient mice. Studies will be directed towards understanding how limiting the expression of Class II molecules alters the positive and negative selection, peripheral survival, and peripheral survival and effector function of CD4+ T cells.
Dr. Levine’s basic science research is focused on defining the role that histone deactylases (HDACs) and heat shock proteins (hsps) play in tolerance of renal ischemia-reperfusion, work that is now funded by the NIH. This work has demonstrated significant renal function protection via HDAC inhibition by drug and by gene knockout which has also been associated with substantial diminution of fibrosis after injury. Further work is investigating which specific HDAC pathways are involved and determining if the site of action is on the kidney or the inflammatory cascade. Additional directions of this work are defining the role that hsps play in renal ischemic damage and whether the expression of hsps is beneficial or detrimental to renal ischemic recovery. Additional work is investigating the role of gender and hormone milieu on the response to renal ischemic injury. Dr. Levine has additional collaborative basic science studies investigating the role of costimulation blockade and cytokine pathway manipulation in rejection or tolerance of limb transplantation in murine models, work that is being initiated with funding from the Department of Defense and is initiated in collaboration with Dr Wayne Hancock and Dr Scott Levin. Additional collaborative work with the Hancock laboratory involves the effects of typical immunosuppression strategies on human regulatory T cells (Treg) after transplantation.
We study the intricate interactions between respiratory viruses, such as parainfluenza and respiratory synctial virus, and the lung innate immune system. We seek to identify viral and cellular factors that drive the development of effective antiviral responses able to control virus replication and dissemination. Our long-term goals are to identify potent viral molecular motifs that trigger the host immune response and to harnness them as adjuvants for vaccination. We are also interested in discovering new determinants of virus pathogenesis that could be targeted to minimize acute and chronic post-viral disease.
Eukaryotic cells are compartmentalized into distinct membrane-bound organelles and vesicular structures, each with its own characteristic function and set of protein constituents. Work in my laboratory is focused on understanding how integral membrane protein complexes are assembled and sorted to the appropriate compartments within the late secretory and endocytic pathways, how sorting and assembly contribute to the biogenesis of specific organelles in several cell types, how these processes impact biological function in the pigmentary, blood clotting, and immune systems, and how they are thwarted by generally rare genetic diseases.
Our primary focus over the past 18 years has been on melanosomes of pigmented cells. Melanosomes are unique lysosome-related organelles present only in cells that make melanin, the major synthesized pigment in mammals. Genetic defects in melanosome constituents or in their delivery to nascent melanosomes result in ocular or oculocutaneous albinism, characterized by lack of pigmentation in the eyes and or skin and concomitant visual impairment and susceptibility to skin and ocular cancers. Melanosomes are among a number of tissue-specific lysosome-related organelles that are malformed and dysfunctional in a group of rare heritable disorders, including Hermansky-Pudlak and Chediak-Higashi syndromes, and pigment cell-specific proteins that localize to melanosomes are targets for the immune system in patients with melanoma. In an effort to understand the molecular basis of these diseases, we are dissecting the molecular mechanisms that regulate how different stage melanosomes are formed and integrated with the endosomal pathway. We use biochemical, morphological, and genetic approaches to follow the fates of melanosome-specific and ubiquitous endosomal and lysosomal proteins within pigment cells from normal individuals or mice and disease models. Using these approaches, we are (1) outlining protein transport pathways that lead to the formation of these unusual organelles, (2) dissecting biochemical pathways that lead to their morphogenesis, and (3) defining how these processes are subverted by genetic disease. Current efforts focus on how factors that are deficient in patients and mouse models of the genetic disease, Hermansky-Pudlak syndrome, impact melanosome biogenesis. We are particularly interested in how these factors contribute to the formation and dynamics of tubular connections between endosomes and maturing melanosomes that facilitate cargo transport, as well as the formation of retrograde membrane carriers that retrieve unneeded proteins from melanosomes.
Because genetic diseases like Hermansky-Pudlak syndrome affect multiple organ systems, we study how similar sorting processes involved in melanosome biogenesis influence other organelles in different cell types. The first involves lysosome-related organelles in platelets called dense granules and alpha granules. When platelets are activated at sites of blood vessel damage, the contents of these granules are released, leading to optimal blood clot formation and platelet activation. Like melanosomes, dense granules are malformed in Hermansky-Pudlak syndrome, and in collaboration with the Poncz, Stalker and French laboratories at CHOP and Penn we are studying how dense granule contents are delivered within platelets and their precursors (megakaryocytes). Studies in collaboration with the Poncz and French labs also address the contents and secretion of alpha granules and their disruption in human bleeding disorders.
The second cellular system is the dendritic cell, a master regulator of T cell-mediated immunity. Patients with Hermansky-Pudlak syndrome type 2 have recurrent bacterial infections, and we have found that this is at least in part due to defects in the way that dendritic cells sense bacterial infection. Normally, ingested bacteria trigger signaling by innate immune receptors present on the membrane enclosing the bacteria (the phagosome); this signaling is defective in dendritic cells from a mouse model of the disease due to impaired recruitment of the receptors and their signaling platforms. Ongoing studies aim to dissect how phagosome membrane dynamics normally lead to signaling and how this is altered in disease states.
Finally, melanosome precursors in pigment cells harbor intrernal fibrils upon which melanins deposit in later stages. The main component of these fibrils is a pigment cell-specific protein, PMEL. Fibrils formed by PMEL in vitro display features common with amyloid formed in disease states such as Alzheimer and Parkinson diseases. By dissecting how PMEL forms amyloid under physiological conditions, we hope to determine how the formation of "good" and "bad" amyloid differs and thus how the formation of "bad" amyloid might be controlled.
"The Mass Spectrometry Facility is part of the Shared Instrument Facilities of the Department of Chemistry. It provides low and high resolution mass spectra to Penn Chemistry and to other research groups throughout the university community for the determination of elemental composition and purity of a wide variety of compounds."
Investigators interested in using the facility are encouraged to call and discuss their project. Usage fees will be quoted at this time. Fees depend upon the instrument involved in the analysis, complexity of the project, training, etc.
This core provides sophisticated analytical services based on liquid chromatography-mass spectrometry.
MIPG is one of the oldest and longest active research groups in the world engaged in research on the processing, visualization, and analysis of medical images and the medical and clinical applications of these computerized methods. It was formed in the Department of Computer Science, (then) State University of New York, Buffalo, in 1976 by Gabor Herman. Udupa joined the group in 1978. The whole group moved to University of Pennsylvania, its current home, in 1981. Udupa was appointed its director in 1991.
MAGIC (the Meta-Analyses of Glucose and Insulin-related traits Consortium) represents a collaborative effort to combine data from multiple GWAS to identify additional loci that impact on glycemic and metabolic traits.
MAGIC investigators have initially studied fasting glucose, fasting insulin, 2h glucose and HBA1c, as well as performed meta-analysis of more sophisticated measures of insulin secretion and sensitivity. Through these efforts, dozens of loci influencing these traits have been idenfified, a subset of which also influence risk of type 2 diabetes.
The Metabolic Tracer Resource aims to provide consultation and services to IDOM investigators interested in using stable isotope labeled tracers (typically carbon-13 or deuterium) in cell-based, animal and human metabolic studies.
The Resource offers analysis of stable isotope enrichment of glucose, glycerol, fatty acids and amino acids in samples from metabolic tracer studies. These data can then be used to calculate rates of turnover, synthesis, production or recycling.
The Resource is currently located in room 12-171A Translational Research Center (TRC).
The Microbial Culture and Metabolomics Core features facilities and equipment for the aerobic and anaerobic culture of microbial species in both batch and continuous systems as well as services for targeted metabolomics. The core offers training and usage for all of these equipment as well as consultation towards experimental design and method development of microbial culture studies. Additionally, the core offers anaerobic culture services; working with the researcher, the core will purchase, receive, and revive strains from commercial culture collections (i.e., ATCC, DSMZ). The core will prepare glycerol stocks, liquid cultures, or gavage-ready suspensions for inoculation of animals with pure or define-mixed microbial communities.
The Human Intervention Core offers a wide array of services to assist with the design and implementation of microbiome studies. The core can assist with longitudinal studies as well as pilot studies. Pilot studies can be rapidly implemented with human intervention core staff, project managers and research coordinators, to conduct these studies."
"Please fill out this form and send to: firstname.lastname@example.org and email@example.com
"The goal of the Mixed Methods Research Lab (MMRL) in the Department of Family Medicine and Community Health is to foster the use of qualitative and mixed methods research methodologies with a focus on integrating key stakeholder perspectives and goals into research designs. The MMRL works with investigators to provide conceptual and technical support for community based and clinical research questions. Qualitative, mixed methods and action research are uniquely suited to capture the contextual, socio-cultural, and experiential factors that contribute to health disparities.
The MMRL offers consultation, training, and staff support at all stages of the research process, including project and proposal conception, instrument development, budget development, data collection, data management, analysis, and publication/dissemination."
MMRL staff has expertise in a variety of traditional and innovative data collection methods including observation, freelisting, individual interviews, and focus groups. The MMRL primarily uses a modified grounded theory approach to analyzing data. Grounded theory is a methodology that involves iterative development of theories about what is occurring in the data as they are collected. The process develops themes that emerge “from the ground,” based on responses to the open-ended questions developed for the proposed study.
The Molecular Cardiology Research Center (MCRC) was established in 1999 and is devoted to coordinating molecular and cellular research in cardiovascular biology and generating transformational discoveries that directly impact cardiovascular health and disease. The MCRC supports the Penn Cardiovascular Institute’s mission of promoting multi-disciplinary and translational cardiovascular research across schools, institutes, centers, departments and divisions at the University of Pennsylvania.
The Penn Molecular Profiling Facility provides instrumentation and expertise for DNA and RNA profiling. Microarrays and other highly parallel technologies provide the means for measuring the identity and abundance of DNA and RNA for targeted genes, or the whole genome, in a biological sample. The Facility offers a range of cost and performance options suitable for a variety of experimental questions. Molecular assays are critical to many aspects of basic, clinical, and population research, including molecular stratification of patients entering clinical protocols, molecular epidemiological and pharmacogenetic studies, as well as longitudinal follow-up of patients in clinical investigations.
Since molecular technologies and instrumentation are evolving rapidly, the centralization of molecular testing services within this core facilitates utilization of leading-edge molecular analyses by the investigators. Because some assays are used for clinical decisions during clinical trials, tests are meticulously designed and performed with strict attention to the prevention of polymerase chain reaction (PCR) contamination.
The Facility is a fully equipped molecular biology laboratory staffed by experienced individuals in developing and performing molecular biological assays. While the Facility staff performs most of the assays, investigator-performed studies are actively encouraged through the sharing of Facility procedures, individualized training of investigators or their technical staff, and use of core equipment.
The Facility Director and the Technical Director are available to talk with investigators to explore how the services of the facility can enhance or design their specific research projects. We invite investigators to meet with us in the planning stages of their studies, especially before grant submissions, to discuss services that the core can provide, such as budget information and a description of the core for the resources section of the grant, as well as to plan collection and handling of the specimens for the study. The Facility is happy to custom design assays to fit an investigator's needs.
The bioinformatics staff of the Penn Genomic Analysis Core is available to provide experimental design and analyical services to the basic and biomedical research community. Our services include support for Next-Gen Sequencing data as well as all platforms available in the core. We provide services as one-on-one meetings with customized approaches determined by the experimental design and goals of the investigator. We translate experimental goals into statistical, analytical and visual prioritization of genes and pathways.
The Wistar Molecular Screening Facility is a shared resource facility accessible to Wistar and non-Wistar scientists. The mission of the facility is to enable investigators to 1) apply cutting edge technology and unique resources to discover molecular, genetic, and small molecule compounds suitable to further study the functions of poorly understood proteins, signaling pathways, and cells in complex biological processes relevant to human physiology and disease; 2) foster collaborations; and 3) fulfill the long-term translational goal of the Wistar Cancer Center of merging basic mechanisms of cancer biology with disease-relevant themes of early-phase drug discovery and new target identification.
The Shared Resource operates on a fee-for-service basis, providing expertise in bridging automated technology with the development of innovative assays for high-throughput chemical and functional genomic screens. The laboratory strives to possess the flexibility to accommodate diverse biological systems and a variety of investigator-developed assay types. While service is the primary role of the laboratory, the staff will also develop and implement new technology as needed to fulfill the needs of its users. Education and training is also part of the laboratory's mission, as trainees apply high-throughput screening experiments to their investigations. The combinations of these activities will provide scientists opportunities to develop new innovative basic and translational research, preliminary data for hypothesis driven research grant applications, and public-private partnerships.
The Wistar Molecular Screening Facility was developed with support from the Commonwealth of Pennsylvania Department of Community and Economic Development Keystone Innovation Zone initiative, The F. M. Kirby Foundation, The CLAWS Foundation, The Florence & Daniel Green Foundation, The McClean Contributionship, From The Heart Foundation, the Noreen O’Neill Foundation for Melanoma Research, NIH shared instrumentation grants, and an NCI Cancer Center Support Grant.
"The Monell Center is the world’s only independent, non-profit scientific institute dedicated to interdisciplinary basic research on the senses of taste and smell.
At Monell, world-class scientists are unlocking some of the most fundamental mysteries of what makes us human. How do we use our chemical senses to communicate? What are the cellular underpinnings of taste and smell that contribute to the difference between lifelong health and chronic disease? How do our chemical senses shape human nutrition? Which genes are responsible?
Monell’s long-standing interdisciplinary model was itself a scientific experiment when the Center was founded more than 40 years ago. Today, Monell remains a nexus where outstanding scientists from many disciplines work together to focus on a common objective: understanding the mechanisms and functions of taste and smell and how these senses relate to human health. The Center’s integrated research approaches range from basic molecular biology to behavioral neuroscience, from cellular biology to comparative ecology, from analytical chemistry to clinical work with human patients.
Monell scientists are at the forefront of discovery, exploring the senses of taste and smell in order to answer pressing questions about health, behavior, and the environment that we could not even foresee a decade ago."
Our lab focuses on the developmental pathways and factors that are critical for building the cardiopulmonary system. Using a combination of mouse genetics, biochemistry, and genomic analysis, we seek to better understand how the lung and heart develop, how developmental pathways are disrupted in human cardiopulmonary disease, and whether such pathways and factors can be harnessed to promote pulmonary and cardiac regeneration in the adult.
The Mouse Cardiovascular Physiology Core Facility, established in April 2006, is under the leadership of Dr. Tao Wang. Our goal is to aid investigators with the creation of mouse models related to cardiovascular diseases. We provide comprehensive assessments of cardiovascular structure and function using high-resolution echocardiographic imaging tools, which provides a unique and valuable research opportunity for translational research from animal studies to human applications. We deliver on-demand services that reveal important cardiovascular, structural, and functional aspects of mouse models in an efficient and cost-effective manner.
We offer a variety of surgical procedures, mouse models of cardiovascular disease, invasive hemodynamical measurements of pressure and ventricle function, high-resolution ultrasound imaging, and ECG/BP telemetry services for the comprehensive evaluation of cardiovascular phenotypes of transgenic and knockout mice. We perform surgical procedures that may be difficult or time-consuming for investigators without the proper expertise, experience, and/or equipment. Furthermore, we provide surgical training for various mouse models and data analysis for physiological assessment of cardiovascular function.
To offer expertise and services for determining the metabolic and endocrine phenotpyes of mice with diabetes, obesity and related disorders.
To create a database of physiologic, endocrine and metabolic measurements in mice.
The NBIC serves as an incubator for new probes of nanostructure behavior and associated instrumentation development. It is equipped with a suite of scanning probes, opto-electronic/transport tools, and optical probes that are so recently developed as not to be available on commercial instruments. The environment facilitates the development and refinement of new probe-based techniques.
Nano/Bio Interface Center at the University of Pennsylvania is a Nanoscale Science and Engineering Center bringing together researchers from the Schools of Engineering and Applied Science; Arts and Sciences; and Medicine. The NBIC exploits Penn's internationally recognized strengths in design of molecular function and quantification of individual molecules. The Center unites investigators from ten departments to provide, not only new directions for the life sciences, but also for engineering in a two-way flow essential to fully realizing the benefits of nano-biotechnology.
Although there have been major advances in Psychiatry and Neurology, less progress has been made toward understanding nervous system function, specifically the mechanisms underlying behavior. The Penn Medicine Neuroscience Center (PMNC), the Institute for Translational Medicine and Therapeutics (ITMAT), the Center for Sleep and Circadian Neurobiology (CSCN) and the Perelman School of Medicine(PSOM) established the Neurobehavior Testing Core (NTC) for behavioral phenotyping of mice. In addition to serving as a resource for neuroscience researchers, the NTC can be utilized by scientists in other disciplines who are interested in the behavioral consequences of other physiological (e.g., metabolic) disruption.
The NTC offers comprehensive testing of mouse models of disease and experimental compounds. Investigators can select from a broad range of assays that can be tailored to their specific interests. Our assays include tests for Learning and Memory, Circadian and home-cage activity monitoring, Affective disorder-related behaviors, Social interaction, Sensory and Motor function, Drug addiction-related behaviors and electrophysiological recording. The NTC also provides consultation, assistance in writing protocols and data analysis. The NTC can train personnel from an investigator’s lab to perform experiments at a reduced cost. Please contact Dr. W. “Tim” O’Brien at firstname.lastname@example.org or (215) 898-0476 to discuss how the Neurobehavior Testing Core could facilitate your research.
Neurons R Us is a service center provided by the Mahoney Institute of Neurological Sciences at the University of Pennsylvania. We have been supplying neurons for research to the Penn community for over 25 years. The center's Technical Director, Margie Maronski, won Penn's 2008 Models of Excellence award for her work providing outstanding cultures to Penn researchers.
Advantages of buying from us
• Low cost
• On campus
• Mouse and rat
• Hippocampus and neocortex - other tissues upon request
• Healthy, longer lasting cultures
• Provided in dishes, wells or in suspension; with or without glia
• Expert advice and troubleshooting
• "Made to order" cultures upon request, e.g. transgenics, other strains
The NGSC offers ultra high throughput sequencing services for the PSOM research community. We offer library quality assessments, sequencing, and optional preliminary data analysis for a wide variety of experimental protocols including ChIP-seq, RNA-Seq, HITS-CLIP, miR-Seq, exome capture, and BIS-seq. We offer limited library preparation services, but can advise on library preparation techniques. We have two Illumina hiSeq2000s for large-scale sequencing and a MiSeq for sample evaluation or library testing. To get started, visit our website, create an account for yourself, then create a new experiment and we will contact you.
The Nucleic Acid/Protein Research Core Facility, located on the 9th floor of the Abramson Building, provides a centralized source for specialized services, technical expertise and reagents to support investigators' molecular biology research needs. These services include DNA sequencing analysis, fluorescent fragment analysis (microsatellite genotyping), oligonucleotide synthesis, microarray services, denaturing high-performance liquid chromatography, Affymetrix GeneChip expression analysis, SNP analysis and RNA analysis.
The CAROT Research Vector Core is a facility that specializes in generating recombinant Adeno-Associated Virus (AAV) vectors for applications in retinal and ophthalmic research. The main objective of the Core is to provide custom-made vectors for basic and translational research. The Core will guide investigators on selection of capsids, regulatory elements and other issues that may impact the results. The core can scale the size of the vector preparation according to the needs of the investigator. All vector lots undergo evaluation to assure purity and high quality. Dr. Shangzhen Zhou an internationally recognized leader in AAV vector production directs the core.
THE CAROT iPS Cell Core is focused on creating a biorepository of cells from individuals with inherited retinal degenerations and on using cells from the repository to establish induced pluripotent stem cell lines that can be differentiated into ocular- and retinal- specific lineages. The use of patient derived iPSC allows the Core to create disease- and patient- specific personalized models of disease. A primary objective of the Core is to use patient iPSC-derived cell models for proof of concept studies and drug screening for new therapeutics. Additionally, the Core will provide training and guide investigators in the creation of iPSC lines and their differentiation into various retinal specific lineages. The Core can also provide liquid nitrogen storage of derived cells. The Core Director, Dr. Jeannette Bennicelli, is a cellular and molecular biologist with expertise in the derivation and manipulation of cell lines as well as design, construction, and testing of therapeutic AAV vectors.
OCR provides education and training, develops policies and best practice processes, and leads quality improvement efforts in areas surrounding human subject research. We strive to assist in creating an interdisciplinary and collaborative research environment for Penn investigators, staff, and external institutional and industry partners.
The mission of the Outcomes Measurement Methods Core Program is to provide investigators, key personnel, and trainees with research collaboration, education, and consultation in the selection and development of measurement tools for translational and clinical research projects.
Initial consultations are provided free of charge. Cost recovery is required for follow-up consultations or long-term collaboration.
The OMMC is managed by the Center for Health Behavior Research (CHBR).
The Personalized NSAID Therapeutics Consortium (PENTACON) is a group of 42 scientists from 22 institutions who have decided to test whether a paradigm for the personalization of drug treatment can be successfully developed. They have applied for funding through the National Institute of General Medical Sciences (NIGMS) GLUE grant mechanism.
PENTACON scientists approach the challenge of personalizing chronic drug therapy by focusing on a single class of drugs – nonsteroidal anti-inflammatory drugs (NSAIDs), initially exploring in detail what factors might contribute to variability in drug response and how that might be reflected by quantitative assays that might predict efficacy or risk.
This involves two major challenges; firstly, the attempt to integrate heterogeneous data – genomics, epigenomics, proteomics, lipidomics, imaging, metabolomics and microbiomics and secondly, the integration of such data from 5 systems – yeast, mammalian cells, zebrafish, mice and humans.
The null hypothesis is that harnessing such information will NOT allow us to provide incremental value to physicians as they decide whether to put a patient on an NSAID and if so which one, at what dose and for how long.
If this hypothesis is rejected for NSAIDs, it will afford a completely novel paradigm for the personalization of medicine.
The mission of the Pathology Clinical Service Center (PCSC) is to promote and facilitate translational research by providing comprehensive blood and tissue-based services to investigators. Among these services are those that traditionally are only provided by Anatomic and Clinical Pathologists in the clinical setting. The Anatomic Division (PCSC-AP) specializes in the analysis of human bio-samples and offers histology, immunohistochemistry, immunofluorescence, in situ hybridization, tissue microarray construction, molecular analysis, digital imaging, multispectral image analysis and assay development. The Transfusion Medicine & Therapeutic Pathology Division (PSCS-TM&TP) encompasses the Apheresis and Infusion Clinic, the Stem Cell Lab, and the Blood Bank, and the Penn Medicine Blood Donation Center. The PCSC-TM&TP operates in compliance with FDA regulations, is accredited by the AABB and FACT, and specializes in the collection, processing, and re-infusion of cellular products, and offering mononuclear cell, whole blood, and plasma collections, elutriation, and infusion of intravenous medications under medical supervision. The Clinical Pathology Division (PCSC-CP) specializes in the analysis of blood and serum samples, including chemistry, microbiology, coagulation, hematology, immunology, and molecular pathology. In addition, PCSC can collect, store, analyze, and annotate research samples for IRB-approved projects.
The Pathology Core Laboratory at the Research Institute at Children's Hospital of Philadelphia unites several core pathology components in one facility. Path Core provides basic histopathology, research immunohistochemistry, tissue microarray, and laser capture microdissection services to researchers at Children's Hospital of Philadelphia and within the surrounding academic community. We offer a full range of histopathology services for both paraffin-embedded and frozen tissue samples including tissue processing, embedding, and cutting. We also perform most standard stains as well as immunohistochemistry, antibody workup, fluorescence, in situ hybridization and TUNEL. Tissue microarrays can be constructed and our staining services may be used on slides acquired from the arrays. Sophisticated imaging instrumentation is available for both bright field and fluorescent microscopy including whole slide scanning. We also host specialized software to analyze, manage, and store data on stained tissues and arrays.
Pemphigus vulgaris (PV) is a potentially fatal disorder in which autoantibodies against desmosomal cell adhesion molecules known as desmogleins cause blistering of the skin and mucous membranes. Our laboratory is interested in better understanding pathogenic mechanisms in this model organ-specific autoimmune disease, from both the immunologic and cell biologic perspectives.
A fundamental question in organ-specific autoimmune disease is why the immune system breaks tolerance against only a limited number of self-antigens. We have cloned B cell repertoires from PV patients to understand how they developed desmoglein autoreactivity. We have identified shared VH1-46 gene usage in anti-desmoglein 3 B cells from different PV patients and defined acidic amino acid residues that are necessary and sufficient to confer desmoglein 3 autoreactivity. These VH1-46 B cells are autoreactive to the disease antigen in the absence of somatic mutation or require very few mutations to develop autoreactivity, which may favor their selection early in the immune response. Common VH gene usage is significant, because it may indicate common mechanisms for developing autoimmunity in PV. Ultimately, shared structural elements of the PV B cell repertoire (e.g., VH or CH gene usage) may lead to safer targeted therapies for pemphigus. Ongoing projects aim to identify potential foreign antigenic triggers of the desmoglein autoimmune response in pemphigus, to identify the B cell subsets that produce the pathogenic autoantibodies, and to develop effective targeted therapies.
Our laboratory is also investigating the cell regulatory pathways that promote desmosomal adhesion. We have shown that the p38 MAPK/MK2 axis is a critical regulator of desmosomal adhesion in keratinocytes and that inhibition of this pathway can ameliorate pemphigus skin blistering. Ongoing projects are studying the regulation of desmosomal adhesion and desmosomal protein expression in keratinocytes to better understand how anti-desmoglein antibodies cause the loss of cell adhesion and how we might interfere with these pathways to improve disease.
The Penn Cardiovascular Institute (CVI) is a multi-disciplinary group of researchers and physicians dedicated to scientific discoveries and medical breakthroughs in heart and vascular care. Penn CVI focuses on translational research, which means taking basic research on the heart and using it to develop new clinical devices and treatments for cardiovascular disease.
Bioinformatics at the University of Pennsylvania encompasses research, service, and education. The Penn Center for Bioinformatics (PCBI) is a base of operations that houses, nurtures, and catalyzes bioinformatics and computational biology research on campus. Experts from the School of Medicine and across the Penn community, PCBI members conduct independent research, but also consult and collaborate with other Penn faculty to contribute to research programs and Center grants. PCBI partners with bioinformatic cores on campus by communicating faculty needs and through its research. Finally, PCBI provides a home, teaching, and research projects for the Genomics and Computational Biology Graduate Group.
Penn Chemistry NMR Facility provides researchers in the Chemistry and Materials Science and Engineering department access to state-of-the-art instrumentation for high resolution NMR spectroscopy. The Facility provides users extensive training to use spectrometers without supervision and expert advice/consultation on advanced applications of NMR spectroscopy to solve research problems.
At present, the Facility operates ten high resolution NMR spectrometers (300-600 MHz) of varying capabilities located in the Chemistry building at the corner of 34th and Spruce street, Philadelphia, PA."
"Penn Chemistry NMR Facility provides limited solution NMR services (data acquisition and spectrum/structure analysis) to other departments/centers of University of Pennsylvania based on hourly charges. However, these services will be limited to the availability of instrument time and personnel.
NMR Facility accepts service samples from outside academic and industrial customers based on per hour charges.
The Penn Gene Targeting Core and Laboratory provides a truly complete knockout and knockin mouse service. In addition it provides all steps necessary for generation of knockout and knockin mutations in human embryonic stem cells (human ES cells) and human induced pluripotent stem cells (human IPS cells). For overview see Main Services below and for details see here. Depending on each project, PGT is using classical gene targeting methods or the revolutionary CRISPR/Cas9 – based system or a combination of both:
• targeting vector design and construction
• CRISPR/Cas9 design and construction
• electroporation of the targeting vectors and/or CRISPR/Cas9 guide RNAs into mouse ES cells or human ES or IPS cells
• PCR/Southern genotyping and karyotyping of the resulting ES/IPS clones
• targeted mouse ES cell injection into blastocysts (usually together with the Transgenic and Chimeric Mouse Facility)
It also provides general genomic Southern/PCR services for genotyping of mouse tails as well as any cell type from which sufficient genomic DNA can be obtained (human ES cells, human iPS cells, mesenchymal stem cells and others).
Genomics represents the transformation from "What is it?" to "What are its organizing and generative principles?" in the scientific journey to understand the complex networks that comprise living organisms and populations. The prime mission of the Penn Genome Frontiers Institute is to be at the forefront of this scientific transformation.
Based at the University of Pennsylvania, PGFI is a university-wide institute dedicated to the advancement of the interdisciplinary field of genomics research. PGFI fosters collaborations and scientific exchange across biology, veterinary medicine, pharmacology, medicine, genetics, microbiology, engineering, physics, chemistry and psychology.
Towards its mission, PGFI pursues four key objectives:
• To lead the development of new quantitative genomic technologies, particularly in the area of in vivo genomics
• To promote genome-scale interdisciplinary research
• To foster integrated genomics education and training
• To assist the incorporation of genomic technologies in biomedical research
The Penn Gnotobiotic Mouse Facility (PGMF) provides centralized germ-free and gnotobiotic mouse services. The PGMF maintains several common strains of germ-free mice that are available upon request, and provides re-derivation services for generating customized germ-free and gnotobiotic mouse strains. In addition, the PGMF offers the Penn research community access to isolators for utilizing germ-free and gnotobiotic mice during IACUC-approved experimental procedures. To further meet the needs of investigators, the PGMF provides technical support required for various experimental procedures.
• Advance our knowledge of the basic immunology of inflammation, autoimmunity, cancer, transplantation and infection and to translate this new knowledge to novel strategies for diagnosis, prevention and therapeutic intervention.
• Foster collaborations and further strengthen interactions among the Penn community of immunologists.
The Penn Medicine Academic Computing Services (PMACS) organization was recently formed through the consolidation of several of the largest groups on campus providing computing services to departments, centers and institutes. The PMACS team now consists of approximately eighty information technology professionals providing services such as desktop support, server administration, storage management, high performance computing, software development, data base development, vendor application deployment/support and staff leadership. This new organization will continue to evolve and grow to meet the education, research and administrative computing needs of the entire Perelman School of Medicine.
The Penn Medicine BioBank assists researchers in need of access to human samples. Our facility banks blood specimens (i.e., whole blood, plasma, serum, buffy coat, and DNA isolated from leukocytes) and tissues (i.e.,formalin-fixed paraffin embedded, fresh and flash frozen). All studies requesting specimens must have IRB-approval for access to human samples. Additionally, each study must apply to the Penn Medicine BioBank Steering Committee for approval. Requests for blood and tissue will be reviewed by a panel of scientists and ranked. Priority will be given to those investigators with current NIH funding, but will be made available as recommended by the Steering Committee. These access decisions will be made on an individual basis, though the committee may consider some or all of the following issues: the nature and scope of the project, how much sample is requested, and the impact on Penn Medicine.
The PennCHOP Microbiome Program supports research across a wide spectrum of topics, with the goal of devising methods for improving human health by manipulating microbial populations. Teams at UPenn and CHOP were leaders in the Human Microbiome Project, the largest project in the history of microbiology. Studies are now expanding to link up microbiome research with myriad diverse areas of basic, translational and clinical research.
Microbiome research at Penn and CHOP includes analysis of multiple human body sites including gut, airway and skin. Microbiome studies have also been carried out extensively using animal models, including germ free (gnotobiotic) mice. Additional ongoing projects seek to translate insights in microbiome analytical methods to clinical diagnosis.
The Pennsylvania Muscle Institute is an interdisciplinary group of research investigators. Our goal is to discover the the mechanisms of muscle function, muscle disease and motile biological systems through innovative and cross-disciplinary research, and to apply these discoveries to new therapies.
We aim to develop state-of-the art technologies for the study of muscle and motile systems, while providing education and training in muscle biology and motility to scientists, physicians, and students.
Research is conducted using biophysics, biochemistry, genetics, physiology and ultrastructure to understand: cell migration and intracellular transport; molecular motors; cell division; muscle contraction and development; muscle pathologies and therapies targeted to muscle disease.
The PMI is prominent in technological and methodological development for these investigations especially in advanced light microscopy, structural spectroscopy, nanotechnology, biochemical kinetics, image processing, molecular biology, and viral gene targeting.
The University of Pennsylvania is the oldest and one of the finest medical schools in the United States. Penn is rich in tradition and heritage and at the same time consistently at the forefront of new developments and innovations in medical education and research. Since its founding in 1765 the School has been a strong presence in the community and prides itself on educating the leaders of tomorrow in patient care, biomedical research, and medical education.
The PET Center is dedicated to continuing the advancement of molecular imaging and seeks to build a network of collaborators to conduct translational research using existing and new radiotracers to help better understand the diagnosis, physiology and treatment of multiple diseases.
We strive to educate referring clinicians and their patients about the emerging benefits of PET/CT diagnostic procedures, other radiotracer imaging methods and radionuclide therapies as tools in their research and clinical practice.
The PET Center is committed to providing opportunities and mentoring for individuals interested in pursuing work or collaborations within the molecular imaging field.
The Protein Expression Facility is a shared resource laboratory that provides Wistar Cancer Center Members and non-Wistar scientists technical assistance with viral vector preparation and the expression and purification of recombinant proteins. The Facility has greater than 20 years of experience in recombinant protein expression with special expertise in the use of baculovirus expression systems (BVES). The Facility offers the following services:
1. Recombinant plasmid DNA engineering
2. Viral vector production (i.e. baculovirus and retrovirus)
3. Analytical and preparative scale expression of nascent or epitope-tagged recombinant proteins
4. Protein purification
These goals are accomplished by a centralized laboratory with dedicated, experienced staff, which enables high-throughput, economy of scale, virus preparation and protein expression services, including quality assurance and control procedures to ensure efficient, consistent production and purification of recombinant proteins and viral vectors. Many recombinant proteins produced by the facility have been used for crystallization efforts, analytical biochemistry studies designed to investigate enzymatic properties, structure-function relationships between protein-protein, protein-nucleic-acid, and protein-small molecule interactions, custom antibody production, experimental cancer vaccines, and development of miniaturized assays for small molecule screening.
The facility is supported in part by an NCI Cancer Center Support Grant and a grant from the NIH National Institute of Aging (PO1 AG031862).
The Protein Core Facility (PCF) at CHOP addresses the overwhelming need for the technological resources to identify, produce and characterize new proteins. The PCF has four operating modules available: Protein expression, Characterization, Protein-Protein Interactions, and Proteomics. While many of our services are routine, we are also committed to collaborating with the CHOP community to overcome difficult research obstacles. We strongly encourage CHOP researchers to bring their research needs to our attention, so that we can try and provide solutions.
PROTEIN EXPRESSION AND PURIFICATION: With the advent of high-throughput DNA sequencing technology and the identification of an increasing number of genes and ORF's, there is an increasing demand for fast and efficient protein production. While some proteins can be expressed in bacteria, other proteins require other expression systems. These might include proteins that require certain chaperones for folding, are toxic to bacteria, contain multiple disulfides, have glycosylation sites, or require other extensive post-translational modifications for their activity. The PCF provides protein production in insect cells (sf9, sf21) using the Baculovirus expression system. We also offer assistance with expression of bacterial proteins or in vitro translation. For purification of the recombinant proteins we offer affinity, ion exchange and size exclusion chromatography.
PROTEIN CHARACTERIZATION: In addition to offering expression services, the PCF provides analyses such as mass spectrometry, gel electrophoresis, analytical and/or preparative chromatography, spectroscopy (fluorescence, circular dichroism, ultraviolet-visible), ultracentrifugation, and phosphorimaging. We also offer assistance in refolding recombinant proteins.
PROTEIN-PROTEIN INTERACTION: The identification of interacting protein partners is fundamental to the understanding of signaling networks and drug-discovery. The PCF has a number of tools for identifying new protein-protein interactions. Options include the SELDI protein-chip analyzer, analytical ultra-centrifugation, and Surface Plasmon Resonance (Biacore). We are also implementing, in collaboration with Invitrogen, an new protein-interaction array service. Once new partners are detected, we offer protein identification using mass spectrometry. Please consult with Steven Seeholzer for more information regarding these techniques.
PROTEOMICS: The PCF is committed to providinging the latest technologies in mass-spectrometry, multi-dimensional chromatography, protein-arrays etc. Utilizing these tools will enable us to uncover more new protein sequences and protein-protein partners so that we might have a better understanding of proteins within specific networks and at the center of pediatric diseases. This knowledge will be critical if we are to successfully understand and treat medical problems that arise at the biochemical level.
The Wistar Proteomics Facility provides mass spectrometry (MS) and sequence analysis of proteins and peptides at maximum sensitivity using state-of-the-art instruments and methods.
The most commonly used services are identifications of either purified proteins or complex protein mixtures, such as sub-proteomes or complete proteomes, using electrospray ionization tandem mass spectrometry (ESI MS/MS). Typically, either individual bands are excised from 1-D SDS gels, or the entire gel lane is analyzed by slicing it into uniform fractions followed by trypsin digestion and nanocapillary HPLC interfaced directly with hybrid ion trap mass spectrometry (Gel/LC-MS/MS). Data is analyzed and filtered to produce low false-positive rates. Several options are available for quantitatively comparing protein changes in related samples, and additional options will be implemented in the future.
Complementary services include reverse-phase microbore HPLC peptide mapping with UV detection and mass measurements of intact peptides and proteins using MALDI MS or ESI MS. Posttranslational modification (PTM) analyses including identifications of specific modified residues also are provided, although investigators should recognize that in most cases these studies are quite complex and require substantial effort. These studies, as well as analyses of complex protein mixtures, usually require preparation of custom sequence databases and/or custom data analyses, which can be provided by the facility as needed.
The Proteomics Core Facility in the Penn Genomics Institute is a service and collaborative research resource that balances applied proteomics research with the development of new and improved methods for protein identification, characterization, and quantification. The facility encourages collaborations that apply the tools of proteomics to cutting edge biomedical research.
The Proteomics Core Facility is a center not only for services but also for basic and collaborative research and development of two-dimensional gel electrophoretic - and mass spectrometric-based techniques. Prospective users are encouraged to make their inquiries either by e-mail (email@example.com), or stop by our facility on the eighth floor of BRB II/III.
The purpose of the Psychiatric Genomics Consortium (PGC) is to unite investigators around the world to conduct meta- and mega-analyses of genome-wide genomic data for psychiatric disorders.
Today, our mission is to provide a support system for coordinators within the Department of Radiology and:
• Build a strong research coordinator team within the Department of Radiology
• Set up a network for research coordinators where assistance can be provided in the orientation of new research coordinators, and in the education of co-workers through the sharing of expertise (ex., MR, CT, and/or PET)
• Gain knowledge and further careers within the Department of Radiology
• RADCORE also houses an IND Support Service that manages a portfolio of regulatory support for investigational diagnostic imaging probes requiring IND or RDRC regulatory approval and support. This service is managed by Kathleen Thomas, whom investigators interested in investigational tracers should contact. See also PET Center for further information about investigational PET imaging probes.
The Rader laboratory is focused on two major themes: 1) novel pathways regulating lipid and lipoprotein metabolism and atherosclerosis inspired by unbiased studies of human genetics; 2) factors regulating the structure and function of high density lipoproteins and the process of reverse cholesterol transport and their relationship to atherosclerosis. A variety of basic cell and molecular laboratory techniques, mouse models, and translational research approaches are used in addressing these questions.
"The assay service has proven essential for current research in the DRC and Penn community. The core used to focus mainly on rat and human insulin, glucagon and C-peptide to a diverse, high-volume and cost-effective service. Over 50 different diabetes and endocrinology-related markers can be assayed.
In conjunction with the Clinical and Translational Research Center (CTRC), we are now offering multiple analyte (multiplex) services. As part of a collaborative initiative, Dr. Collins initiated and established Luminex IS100 multiplex ELISA services. This system uses cell-sorting technology to measure multiple proteins simultaneously. This technology will be of great use for investigators studying transgenic mice, where sample volumes are low. In addition, the multiplex platform allows for screening of human cohorts in disease research particularly of small volume in repeated sampling protocols.
The objectives of the Radioimmunoassay and Biomarker Core includes:
• delivery of new services to existing and new investigators
• development of informatics infrastructure for efficient delivery of service
• engage proactively in outreach to the DRC/PENN research community to enhance efficiency, cost-sharing and increase users of Biomarker Core services."
The assay services listed are not an exhaustive list but rather a list of assay services we have provided in the past. Please contact the RIA/Biomarkers core if you would like to assay for an analyte that is not listed. We can help you find the appropriate kit and provide the assay service.
The goals of the Recruitment, Outcomes and Assessment Resource (ROAR) are to develop resources for population and clinical/transitional research that can enhance collaborative, multidisciplinary population research; enable observational, behavioral, clinical translation and interventional studies; and avoid inefficiency in the development and execution of these studies.
The ROAR, which is led by Dr. Karen Glanz, is comprised of two coordinated components: one for Recruitment, Retention and Outreach and a second for Research Implementation.
CAROT is an integral part of the Scheie Eye Institute, one of the oldest and most reputable ophthalmology clinics in the USA. This institute has an established history of successfully executing clinical trials using a diverse patient population.
CAROT offers comprehensive testing facilities to complete most study protocols in compliance with several health authority standards. As a pioneer in the field of gene and cell therapy, CAROT contains unique endpoint measures such as mobility tests, functional magnetic resonance imaging (fMRI) and adaptive optics scanning laser ophthalmoscopy.
CAROT also manages clinical, regulatory and trial site services to guide investigators through the clinical and market authorization process, with speed, accuracy and safety.
The mission of the Research Ethics Program is to provide investigators, key personnel, and trainees with research collaboration, education, and consultation that address ethical issues in the design and conduct of translational and clinical research. We are primarily engaged in contributing to the CTSA's research ethics educational needs, and we provide consultation services for CTSA and other researchers facing ethical issues in planning or performing their studies. We also have research interests in identifying new and emerging ethical issues in translational research and are looking for collaborative opportunities to better understand this research paradigm.
The Research Instrumentation Shop is non-profit, shared resource machine shop of the University of Pennsylvania, Perelman School of Medicine. Its mission is to assist University faculty in the design and construction of both laboratory and clinical instrumentation. The staff is comprised of mechanical and optical specialists and is experienced with working with scientists to design and construct custom research clinical instrumentation and apparatus.
The use of both genetic and molecular approaches to the study of virus-host interactions in vivo provides us with insight into the processes that determine the susceptibility and resistance of individuals to viral infection and virus-induced cancer (approximately 20% of human cancers). Our interests lie in determining why viruses infect specific hosts and how in turn, host genes confer resistance to this infection. Our lab studies 2 different types of viruses, retroviruses like mouse mammary tumor virus (MMTV) and murine leukemia virus (MLV) which cause cancer in mice, and the new world arenaviruses, which cause hemorrhagic fever in humans.
The genetics of susceptibility is easily studied with naturally-occurring pathogens in inbred and genetically-manipulated mice. MMTV is an endemic oncogenic retrovirus that has been an infectious agent in mice for > 20 million years, while MLV has been in mice ~ 3 million years. Infectious MMTV is passed from mothers to offspring through milk and first spreads in lymphoid cells before infecting mammary epithelial cells; MLV is probably also milk-transmitted. These viruses thus serve as models for the human milk-borne retroviruses HIV-1 and HTLV1. MMTV causes breast cancer and MLV causes lymphomas when the viral genome inserts next to cellular oncogenes by activating their expression. Our studies focus on understanding the mechanisms that determine susceptibility to MMTV infection and virus-induced mammary tumors and we have identified a number of genes and mechanisms that confer resistance to infection by MMTV and MLV.
Genes of the immune system play a major role in susceptibility to infection, and one gene which we recently discovered is involved in the control of MMTV and MLV infection is Apobec3. All mammals encode Apobec3 genes which play a role in intrinsic cellular immunity to a number of viruses, including human immunodeficiency virus type 1. APOBEC3 proteins are packaged into virions and inhibit retroviral replication in newly infected cells, at least in part by deaminating cytosine on the negative strand DNA intermediates. We found that mouse APOBEC3 protein is packaged into MMTV and MLV particles in vitro and dramatically reduces viral titers. Most importantly, APOBEC3 knockout mice are more susceptible to MMTV and MLV infection compared to their wild type littermates. These findings indicate that the APOBEC3 provides protection to mice against retroviral infection and represent the first demonstration that it functions during retroviral infection in vivo. We are currently studying how genetic variation in the mouse APOBEC3 genes affects their ability to inhibit infection and whether APOBEC3 can be used as an anti-retroviral therapeutic target.
We have recently extended our studies to new world arenaviruses like Junín virus. These viruses are endemic in new world rodents in South America and are spread to humans via aerosolization. Interestingly, both Junín virus and MMTV use transferrin receptor 1 (TfR1) for entry. We are currently studying how MMTV and Junín virus use TfR1 to enter cells and how the iron metabolic pathway intersects with infection by these viruses. In addition, we are studying different host genes that confer resistance or susceptibility Junín virus, and whether polymorphisms in these genes in humans alter infection. These studies will help us identify host molecules involved in cell- and disease-tropism and help us to develop new anti-viral therapies.
My laboratory is particularly interested in understanding how angiogenesis inhibitors act to limit endothelial cell activation and angiogenesis, and how they might be used therapeutically to treat cancers. Specific projects include:
i) Understanding why Down syndrome individuals are protected against cancer and the role of the calcineurin inhibitor, DSCR1 in suppressing VEGF-mediated angiogenesis;
ii) Identifying new cell extrinsic tumor suppressor functions of p53 and p19ARF: regulation of the endogenous angiogenesis inhibitors thrombopsondin-1 and endostatin;
iii) Investigating a novel role for the endogenous angiogenesis inhibitor thrombospondin-1 in mediating oncogene-induced senescence;
iv) Immune surveillance and the role of the endogenous angiogenesis inhibitors thrombospondin-1 and endostatin in tumor immunity.
My lab is interested in uncovering molecular and cellular mechanisms used by the host to defend itself against bacterial pathogens and how bacterial pathogens evade or manipulate host defenses.
We utilize the intracellular bacterial pathogen Legionella pneumophila, causative agent of the severe pneumonia Legionnaires' disease, as our primary model. Legionella has evolved numerous mechanisms for modulating eukaryotic processes in order to facilitate its survival and replication within host cells. The ease with which Legionella can be genetically manipulated provides a powerful system for dissecting immune responses to bacteria that differ in defined virulence properties and for elucidating mechanisms of bacterial pathogenesis.
A major focus of our lab involves understanding how the immune system distinguishes between virulent and avirulent bacteria and tailors appropriate antimicrobial responses against virulent bacteria. One key immune pathway involves the inflammasome, a multi-protein cytosolic complex that activates the host proteases caspase-1 and caspase-11 upon cytosolic detection of bacterial products. These caspases mediate the release of IL-1 family cytokines and other inflammatory factors critical for host defense, but overexuberant activation can lead to pathological outcomes such as septic shock. We are currently pursuing how inflammasomes are differentially regulated in mice and humans in response to bacterial infection, as mice and humans differ in several key inflammasome components.
We are also uncovering how the immune system successfully overcomes the ability of pathogens to suppress host functions critical for immune defense. We recently found that infected macrophages circumvent the ability of Legionella to block host translation by synthesizing and releasing key cytokines that instruct bystander uninfected cells to generate an effective immune response. We are defining additional mechanisms that mediate communication between infected and bystander cells and promote eventual control of bacterial infection. We also examine immune responses to other bacterial pathogens with the goal of identifying shared and unique features of innate immunity and bacterial virulence. Insight into these areas will advance our understanding of bacterial pathogenesis, how the innate immune system distinguishes between virulent and avirulent bacteria and initiates antimicrobial immunity, and will ultimately aid in the design of effective antimicrobial therapies and vaccines.
The Singh Center is centered around four major research facilities, all featuring state-of-the-art equipment for nanoscale characterization, measurement, and fabrication: the Quattrone Nanofabrication Facility, the Nanoscale Characterization Facility, the Scanning and Local Probe Facility, and the Material Property Measurement Facility.
The following connected sections comprise the major components of the building:
• A 10,000 square-foot next-generation Cleanroom Facility for micro/nanofabrication, including tooling for nanoscale and soft materials integration and a novel nano/bio bay serves as the home of the Quattrone Nanofabrication Facility.
• A 10,000 square-foot advanced underground facility designed for temperature stability and excellent isolation from vibrational, acoustic, and electromagnetic noise serves as home of both the Nanoscale Characterization Facility and the Scanning and Local Probe Facility.
• A Property Measurement Facility provides state-of-the-art measurement capabilities in magnetometry, optics, electrical and thermal transport.
• 18,000 net square feet of space for other shared facilities and general laboratories housed in an adjoining three story structure; a glass-enclosed galleria with views into the cleanroom; conference rooms; and a forum for meetings.
The building houses a large suite of high-performance equipment for nanotechnology research, including electron and scanning probe microscopy, cleanroom tools, electron beam lithography, and several materials synthesis and characterization instruments.
The multi-user facilities are vital to the research and educational programs at Penn and are leveraged by partner institutions and local industry within the Mid-Atlantic region. Unifying these central resources fosters the exchange of scientific ideas and the development of nanoscale science and technology, brings together crosscutting capabilities and the staffing to support these tools, and provides the modern infrastructure necessary to establish a regional center for nanotechnology.
The SAIF combines state-of-the-art instrumentation and a nationally recognized staff to assist investigators with a wide range of imaging based experimental approaches. The SAIF currently provides a comprehensive suite of imaging modalities including:
• Magnetic resonance imaging (MRI) and spectroscopy (MRS)
• Optical imaging (including bioluminescence, fluorescence, and near-infrared imaging)
• Computed tomography (CT)
• Positron emission tomography (PET)
• Single photon emission computed tomography (SPECT)
• Ultrasound (US)
In addition, dedicated housing is available for mice and rats undergoing longitudinal imaging studies. Ancillary facilities and resources of the SAIF are devoted to chemistry, radiochemistry, image analysis and animal tumor models, including assistance with animal handling.
These studies are performed on a wide range of biological samples including small animals (cats, rabbits, rats, mice), tissue specimens, cultured cells and tissue extracts.
This facility includes a conveniently located, well equipped surgery room used for preparing the animals for MR exams and a wide assortment of supporting equipment, i.e. anesthesia machines, MR compatible vital signs monitors (SA Instruments), infusion pumps (Harvard), heating pads, etc. A variety of perishable supplies used in animal preparation are also provided by the facility.
The PET Center operates various PET, SPECT, and CT scanners for different research and scanning needs.
The Optical/Bioluminescence Sub-Core of the SAIF provides the capability to perform cellular and molecular non-invasive in-vivo bioluminescence, near-infraredfluorescence and Cerenkov imaging.
The instrumentation allows sensitive, non-invasive molecular imaging for a variety of applications including detection and quantification of various bioluminescent or fluorescent reporter-expressing cells or tissues (in culture or in small animals).
The facility currently houses a Perkin Elmer IVIS Lumina II, two LI-COR Pearl Impulse Imagers and two Perkin Elmer IVIS Spectrums. The Facility offers assistance with experimental design, regulatory approval, troubleshooting, data management, analysis and display.
The Ultrasound Sub-Core of the SAIF offers an array of research services for pre-clinical research including quantitative image analysis and consultation.
Our state-of-the-art ultrasound scanners are available as a resource for conducting your research studies. This rich resource for ultrasound imaging is available at nominal hourly fees for various categories of study.
Ultrasound Research Services provides services to a host of groups working on diverse projects such as the measurement of angiogenesis, vascularity, tissue elasticity, the effects of various pharmaceuticals on these measures and more. Such research encompasses a variety of clinical areas including radiology, oncology, cardiology, gynecology, and hematology, among others.
The work in my laboratory is centered on the core binding factor (Runx1-CBFβ) and its roles in hematopoietic stem cell (HSC) formation and function. We study how HSCs form in the embryo, the step at which HSC formation is dependent on Runx1-CBFβ, the biochemical functions of Runx1-CBFβ, and how mutations in the genes encoding Runx1-CBFβ generate pre-leukemic stem cells. A more recent line of investigation is to determine the role of inflammatory signaling in HSC formation.
The Stem Cell and Xenograft Core (SCXC) is a comprehensive resource laboratory that integrates a viable tissue bank of normal human hematopoietic cells and hematopoietic malignancies with a full range of xenograft services.
The SCXC is committed to facilitating and promoting translational research involving viable primary human hematopoietic tissues. Our core offers adult whole bone marrow from healthy donors and umbilical cord blood. Mononuclear and CD34+ cells from normal bone marrow and cord blood are available, and other cell fractions can be provided by arrangement. We maintain a large tissue bank of cells from hematopoietic malignancies including AML, ALL, CML, MDS and MPDs. All samples are fully annotated and frozen as viable cells. We also offer access to an immunomagnetic cell sorter (Miltneyi AutoMacs). Expertise in primary human hematopoietic stem/progenitor and leukemic cell culture and manipulation is available. For consultation or questions, please contact Martin Carroll.
The SCXC offers a wide variety of xenograft services from training to full-service experiments. The Core maintains a large breeding colony of immune-deficient (NSG) mice for users xenograft studies. We also offer human immune system (CD34-transplanted) NSG mice for a wide variety of studies ranging from gene therapy to HIV. Experimental animals are housed in dedicated BSL-2 animal barrier space equipped for whole body irradiation and all necessary procedures and survival surgeries. Currently established xenograft models include normal human CD34 and leukemia engraftment, human iPS and ES-derived teratomas, human skin grafting, orthotopic human ovarian, hepatic and pancreatic tumor cell injections, renal capsule implantation. We also offer access to a dedicated optical/fluorescence (IVIS Spectrum) imaging system located within the Core's BSL-2 space. For consultation or questions, please contact Gwenn Danet-Desnoyers.
Pennkey required to request services, contact to acquire a guest Pennkey if needed.
Broadly, the lab studies the development and physiology of the mammalian brain. One goal is to define the systems that contribute to specific behaviors, and to understand the mechanisms that underlie these behaviors. Such knowledge may ultimately permit the prevention and treatment of mental illness. Gene-targeting allows the analysis of specific genetic alterations in the context of the whole organism. The ability to add, delete or modify genes is particularly useful in the analysis of complex organ systems such as the brain, where half of all genes are thought to be uniquely expressed.
The lab focuses on the adrenergic nervous system in which norepinephrine (NE) and epinephrine are the classic neurotransmitters. By genetically eliminating the biosynthetic enzyme for NE, dopamine beta-hydroxylase (DBH), mutant mice (Dbh-/-) that completely lack NE and epinephrine were created. These mice are conditional mutants in that NE can be restored to the adrenergic terminals by supplying a synthetic amino acid precursor of NE, L-DOPS. The lab is pursuing several fundamental observations that resulted from the creation of these mutant mice. These include the roles of NE in learning and memory, as well as the neuronal physiology and signaling that underlie these effects. They also include the role of NE in the effects of stress. For each of these, potentially important interactions with other transmitters and hormones is also being explored. Finally, Dr. Thomas is pursuing several novel genetic approaches for producing complementary models to the Dbh-/- mice toward a more complete understanding of CNS adrenergic function.
The primary focus of research in the Abel lab is to understand the cellular and molecular mechanisms of long-term memory storage with a focus on the mammalian hippocampus. One of the hallmarks of long-term memory storage is that it requires the synthesis of new genes and new proteins, which act to alter the strength of synaptic connections within appropriate neuronal circuits in the brain. How are the various signals acting on a neuron integrated to give rise to appropriate changes in gene expression? How are changes in gene expression maintained to sustain memories for days, months and even years? In our lab, we have focused on transcriptional co-activators such as CREB-binding protein (CBP) and p300, leading us to investigate the effects of histone acetylation and other epigenetic modifications in memory storage. Increasing histone acetylation pharmacologically by inhibiting histone deacetylase (HDAC) enzymes during memory consolidation enhances long-term memory. Of particular importance is the identification of genes regulated by epigenetic mechanisms during memory consolidation and after HDAC inhibition using next-generation sequencing technology. Signals from synapses drive the transcriptional processes that are required for memory storage. A major challenge in the study of these synaptic signals is how the pathway specificity of synaptic plasticity is maintained in the face of diffusible second messengers, such as cyclic AMP (cAMP), and diffusible proteins, such as the catalytic subunit of protein kinase A (PKA). We are investigating the role of A-kinase anchoring proteins (AKAPs), which restrict PKA to specific subcellular locations, to define how signal transduction pathways in neurons are able to exhibit spatial specificity.
We are also investigating processes that can modulate the consolidation of long-term memory. For example, the biological function of sleep has remained elusive, but studies suggest that one function of sleep may be to mediate memory storage. First, sleep appears to facilitate the formation of hippocampus-dependent memories, and sleep is increased following training. Second, sleep appears to be regulated by many of the same molecular processes that contribute to memory storage, including the transcription factor cAMP response element-binding protein (CREB) and the PKA signaling pathway. By using conditional genetic approaches and gene expression studies, we are striving to elucidate the machinery underlying sleep/wake regulation and define the role of sleep in the consolidation of long-term memory. Our studies also reveal that sleep deprivation impairs memory consolidation and synaptic plasticity by impairing signaling through the cAMP pathway.
Cognitive deficits accompany many neurological, psychiatric and neurodevelopmental disorders. We are interested in determining how our knowledge of the cellular and molecular mechanisms of synaptic plasticity and memory storage can help us understand the cognitive deficits that are seen in patients with schizophrenia, autism and intellectual disability. Recent evidence suggests that disturbances in specific intracellular signaling pathways may contribute to schizophrenia. Studies in humans indicate that activity within the cAMP/PKA signaling pathway may be increased in the central nervous systems of schizophrenia patients, and our work suggests that this pathway plays a role in endophenotypes of schizophrenia in mice. With these translational approaches, we hope to identify novel targets for the development of new therapeutics to treat psychiatric and neurodevelopmental disorders.
The Children's Hospital of Philadelphia has a long and distinguished tradition of research that has spanned more than 80 years and positioned the Hospital as a world-renowned pediatric research center. The many research breakthroughs at Children's Hospital have improved the lives of countless children not only in the Philadelphia region, but throughout the world.
Research at the Hospital had modest beginnings. The Hospital established its first research laboratory in 1922 as a single room in its basement. By 1931, the Hospital founded the “Society of Pediatric Research” for its expanding base of investigators, who conducted their experiments wherever space permitted.
These beginnings gained significant momentum in 1972 when Children's Hospital designated 70,000 square feet to research and established the Research Institute, the first pediatric research department in the country.
Today, the Hospital's entire research enterprise is organized under the aegis of the CHOP Research Institute and constitutes a separate organizational, administrative and financial entity within the Hospital.
This Research Core provides training and research support in genotyping and quantification of nucleic acids. The Core facility has equipment needed to genotype DNA samples and to measure nucleic acid concentrations in isolation or in tissue samples.
The mission of the IDOM is to support and develop successful approaches to the prevention, treatment, and cure of diabetes mellitus and obesity.
The Wistar Institute is the nation’s first independent institution devoted to medical research and training. The Wistar Institute has evolved from its beginnings as an anatomical teaching museum to its present-day status as an international leader in basic biomedical research.
In 1972, The Wistar Institute was designated a National Cancer Institute Cancer Center in basic research—a distinction it holds to this day.
Wistar discoveries have led to the development of vaccines for rabies, rubella, and rotavirus, the identification of genes associated with breast, lung, and prostate cancer, and the development of monoclonal antibodies and other significant research technologies and tools.
In our lab we study two cognitive disorders: Fragile X Mental Retardation and Alzheimer's disease. To study these disorders we utilize Drosophila models. These models are mutants of the Drosophila homologues of the humans genes associated with these disorders. With these models we are investigating the biochemical functions and biochemical pathways affected by the loss of the disease related proteins that cause phenotypes that are similar to symptoms display by patients of these diseases (see below). Our goals are to gain insight into the underlying causes of the respective disease symptoms as an approach to develop therapeutic strategies to treat these disease as well as to learn more about the basic mechanisms required for normal learning and memory.
The purpose of the Transgenic & Chimeric Mouse Facility is to provide a centralized service to efficiently produce transgenic mice for basic research. This should result in reduction in effort and cost to participating investigators. The facility is located on the basement level of the Clinical Research Building. This facility consists of an animal room and several injection rooms. The injection rooms are fully equipped to carry out the entire procedure of making transgenic mice. The animal room provides housing and breeding space for the mice involved in the transgenic projects. The facility uses sterile food and water as well as autoclaved cages and bedding; all cages are of the microisolator type to limit the spread of colony infection. The entire facility is located behind a microbiologic barrier where admittance is strictly limited and all personnel must wear sterile coveralls, gloves, hats, masks, and boots.
This core provides sophisticated analytical services based on liquid chromatography-mass spectrometry.
Research currently centers on molecular mechanisms of neuron dysfunction, degeneration and death in normal aging and in neurodegenerative diseases (Alzheimer's and Parkinson's disease, frontotemporal dementias with/without parkinsonism, motor neuron disease, etc.). This research uses immunological, biochemical, genetic, molecular and morphological methods to study human CNS and PNS tissue samples (postmortem or surgical), cell lines, synthetic proteins, and transgenic models of neurodegenerative diseases. Dr. Trojanowski is involved in collaborative initiatives between PENN Medicine and the University of Pennsylvania School of Nursing to advance drug discovery, clinical research, and patient care related to Alzheimer’s disease and the Alzheimer's Disease Neuroimaging Initiative (ADNI) to test whether serial magnetic resonance imaging, positron emission tomography, other biological markers, and clinical and neuropsychological assessment can be combined to measure the progression of mild cognitive impairment (MCI) and early Alzheimer's disease.
The goals of the research laboratory are:
• To develop new ultrasound technologies and clinical applications
• To bridge the gap between technology and clinical applications
• To provide ultrasound imaging resources to other research groups within the Penn community and in other institutions
The laboratory consists of a core group of scientists, sonographers and technicians with expertise in ultrasound technology and computer programming. This group works with clinicians in multiple specialties; including radiologists, cardiologists and surgeons. Ultrasound Research Services, an arm of the laboratory, furnishes a state-of-the-art ultrasound scanner dedicated to research and serves the research community. There is a full-time sonographer and a part-time radiologist on staff to conduct clinical and pre-clinical imaging.
The research laboratory has been a valuable resource to several groups working on diverse projects. These include studies involving the measurement of angiogenesis, vascularity, tissue elasticity, contrast agents, and the effects of various physical and pharmaceutical agents on blood flow and tissue vascularity. The studies span a range of clinical areas including research on cancer, cardiovascular disease and musculoskeletal disease.
The Penn Vector Core is a full service viral vector core facility located on the University of Pennsylvania campus. With over a decade of experience in the production of viral-based vectors, the Core has become an important technological resource for investigators, both within and external to Penn, interested in the use of viral based vectors for gene transfer. The main objective of the Core is to provide investigators access to state-of-the-art vector technology for preclinical studies and other basic research applications. Such studies, utilizing carefully designed viral vectors, can provide information critical to the understanding of gene function and development of therapeutic vectors.
The Penn Vector Core specializes in the provision of novel AAV serotype vectors and has the greatest experience in producing novel serotype vectors developed at Penn. AAV1, 7, 8, 9 and rh10 were originally isolated at Penn in the laboratory of Dr. James M. Wilson and first made available to investigators through the Penn Vector Core. Due to its close proximity to the Wilson laboratory, the Penn Vector Core is able to rapidly assimilate new vector technologies and make them available to its users. The Core offers a variety of novel serotype AAV vectors and additional vectors currently under development will be distributed through the Penn Vector. All of the vectors generated by the Penn Vector Core are distributed under material transfer agreement (MTA) to academic, government and non-profit institutions. Corporate users may access novel AAV vector technologies through the Penn co-founded company, REGENXBIO Inc.
The Center for Cellular and Molecular Therapeutics at The Children's Hospital of Philadelphia has established a state-of-the-art cGMP clinical vector manufacturing suite for both adeno-associated viral vectors and Lenti viral vectors, help to realize the enormous promise of gene transfer therapy to address unmet medical needs.
The Core Facility utilizes a patented vector production technology and a highly efficient purification process that utilizes combined column and gradient centrifugation-based process steps. This system has manufactured clinical grade AAV vectors that have demonstrated excellent safety in several clinical studies.
Part of The Center for Cellular and Molecular Therapeutics, the Research Vector Core (RVC) has expanded its capacity to provide infrastructure support for investigators interested in using viral vectors in their research model systems. RVC utilizes molecular biology techniques to engineer and produce recombinant AAV vectors for gene transfer in research experiments or non-clinical studies. RVC staff work closely with investigators to plan and develop vectors for individual project requirements. The RVC has extensive experience in the production of multiple AAV serotypes. Due to its unique manufacturing method, resulting in high productivity, the RVC is able to deliver empty capsid free (<1%) vectors after the purification process. Reporter gene vectors are available directly from inventory. The core is under the direction of Dr. Shangzhen Zhou, a leading expert in AAV vector production. The core employs a team of dedicated technicians to provide research vectors with premium quality.
The central aim in my lab is to understand the genetic, biological, and evolutionary basis of metabolic, cardiovascular, and immune-mediated phenotypes in human populations. To build this understanding, the lab constructs computational and statistical tools grounded in principles of population biology and quantitative genetics and apply them to genetic data collected across thousands of entire human genomes.
My research has answered population genetic questions about recent demographic and selective events in human populations, and more recently I have focused on mapping risk alleles for common diseases, particularly type-2 diabetes and heart attack. I have also contributed to novel statistical approaches for population genetic inference and disease mapping studies, as well as leading the development of next generation sequencing and genotypic assay technologies designed to improve characterization of genetic variation in the human genome.
In the coming years, the lab activities will focus on developing informational and statistical tools which interrogate vast quantities of human genetic association data, together with other important information sources -- gene expression, protein-protein networks, Chip-SEQ, text-mining, epidemiology, and multiple phenotypic measurements in humans -- in order to construct credibly actionable information on pathways responsible for disease susceptibility.
The Vonderheide laboratory combines efforts in both basic research and clinical investigation to advance the understanding of tumor immunology and to develop novel immunotherapies for cancer. The chief hypothesis is that successful approaches in tumor immunotherapy will need to (a) optimize target antigens with regard to clinical applicability and risk of antigen loss, (b) repair host immuno-incompetence in antigen presentation and T cell function, and (c) circumvent immuno-suppressive factors of the tumor and tumor microenvironment.
Our lab focuses on Alzheimer’s disease and other neurodegenerative disorders, aging, and psychiatric disorders including autism and bipolar disorder. Ongoing projects in our lab can be divided into the following three main directions:
• Genetics and genomics of Alzheimer’s disease and other neurodegenerative disorders.
• Informatics and algorithm development for genome-scale experiments.
• Biomarker development for aging and neurodegenerative disorders.
My lab studies coronavirus pathogenesis. We use murine coronavirus, mouse hepatitis virus (MHV) infection of mice as a model system for the study of: 1) acute viral encephalitis; 2) chronic demyelinating diseases such as Multiple Sclerosis and 3) virus-induced hepatitis. We have the important tools of a well-developed animal model system and two reverse genetic systems with which to manipulate the viral genome. Human coronaviruses are primarily respiratory viruses, and include the common cold viruses OC43 and 229E as well as the emerging viruses MERS and SARs that cause severe and life threatening diseases. We are beginning to study human coronavirus interactions with respiratory tract cells. Our long-term goal is to elucidate the viral and cellular determinants of coronavirus tropism and pathogenesis in the brain, the liver and the lung. Much of our current work focuses on coronavirus-encoded antagonists of type I interferon, specifically virus-encoded phosphodiesterase that antagonize the OAS-RNase L pathway. Another direction in our lab is the study of the role of inflammasome related cytokines in viral clearance as well as both acute and chronic MHV induced disease.
The Weljie Lab is located in the Department of Pharmacology at the University of Pennsylvania. Our lab is at the forefront of metabolomics technologies to examine biological problems in a translational medicine context.
Metabolomics is a growing sub-field of systems biology centered on the study of small biological molecules in biological fluids and tissues. Recent research suggests that analysis of metabolite concentrations in living systems is useful in disease diagnosis, prognosis, and predicting drug efficacy in a personalized medicine context.
Our focus is on developing analytical methods to advance research in translational medicine. There is an intrinsic link between metabolism and function of the innate circadian clock system in numerous organisms and disease states, but the exact mechanism by which the clock controls mammalian metabolism is poorly understood. Our work seeks to fill this knowledge gap along with identifying biomarkers of cancer and environmental health.
The "West Center" (or WC3D2, for short) is focused on the application of computational methods to chemical and biological problems, as well as on the development of more powerful computational tools to improve the ability of these methods to produce real world answers.
A major goal of the research in Dr. Wherry's laboratory is to understand the mechanisms of T cell exhaustion during chronic infections and cancer. Our work studying CD8 T cell responses during chronic viral infections has demonstrated that virus-specific CD8 T cells often lose effector functions and fail to acquire key memory T cell properties (i.e. become exhausted). Using approaches including high dimensional flow cytometry, transcriptional and epigenetic profiling and in vivo models we are defining cellular pathways involved in T cell exhaustion and normal memory T cell differentiation. Some areas of considerable current interest for the lab include inhibitory receptors (e.g. PD-1, LAG-3), transcription factors and inflammatory pathways. Blockade of inhibitory receptors such as PD-1 (i.e. checkpoint blockade) is now a major therapeutic approach in human cancer. Ongoing studies are examining the mechanisms of these blockades in preclinical models as well as in humans and are investigating the next generation of immune targets to reverse T cell exhaustion. In addition to T cell exhaustion, the laboratory has major interests in the biology of human T follicular helper cells (TFH). Our studies are interrogating the pathways controlling optimal TFH responses following human vaccination. Finally, additional interests in the lab include intestinal novovirus infection, respiratory infections and co-infections.
The research programs in the Wu laboratory focus on the mutualistic interactions between the gut microbiota and the host with a particular focus on metabolism. Growing evidence suggests that diet impacts upon both the structure and function of the gut microbiota that, in turn, influences the host in fundamental ways. Current areas of investigation include the effect of diet on the composition of the gut microbiota and its subsequence effect on host metabolism related to nitrogen balance as well as its impact on metabolic pathways in the intestinal epithelium, principally fatty acid oxidation. Through a UH3 roadmap initiate grant, he is helping to direct a project investigating the impact of diet on the composition of the gut microbiome and its relationship to therapeutic responses associated with the treatment of patients with Crohn’s disease using an elemental diet. Finally, Dr. Wu is leading a multidisciplinary group of investigators using phosphorescent nanoprobe technology to examine the dynamic oxygen equilibrium between the host and the gut microbiota at the intestinal mucosal interface.
The CAROT Lenti Vector Core is a state-of-the-art production facility, with a Class 7 clean room suite. The production and QA/QC procedures meet the current GMP regulations as enforced by the FDA. Mr. William Chung is the director of the Lenti Vector Core GMP operations. The core group also provides CMC support for regulatory submissions with the assistance of Dr. Ilan McNamara.
The Stem Cell core provides expertise and quality-control reagents for the culture and differentiation of human embryonic stem cells (ESCs) and human induced pluripotent stem cells (iPSCs) to the CHOP and University of Pennsylvania academic communities. The facility maintains five of the new NIH-approved human ESC lines and several human iPSC lines. Stringent protocols are established to:
1. Propagate human ESC and iPSC lines, monitor for maintenance of the pluripotent state and distribute these lines to investigators.
2. Differentiate hESCs/iPSCs into mesoderm, endoderm and their derivative tissues under controlled, serum-free conditions with defined cytokines.
3. Generate iPSCs from human subjects.
Found 274 resource providers .