eagle-i University of PennsylvaniaUniversity of Pennsylvania
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Shin Laboratory

Summary:

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.

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Organisms and Viruses


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Last updated: 2016-03-02T19:14:39.245-05:00

Copyright © 2016 by the President and Fellows of Harvard College
The eagle-i Consortium is supported by NIH Grant #5U24RR029825-02 / Copyright 2016