eagle-i University of PennsylvaniaUniversity of Pennsylvania
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Jordan Laboratory

Summary:

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.

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Organisms and Viruses

  • Akt1 KO ( Mus musculus )

    These mice are at JAX.

  • Akt2 floxed mice ( Mus musculus )

    These mice are from Dr. Morris Birnbaum

  • Akt2 KO ( Mus musculus )

    These mice are from Dr. Morris Birnbaum

  • Eomes fl/fl ( Mus musculus )

    These mice are from S. Reiner.

  • Eomes gfp knockin ( Mus musculus )

    These mice are from S. Reiner / E. Rothenberg.

  • IL-17Acre ( Mus musculus )

    These mice are at JAX.

  • IL-17RFP ( Mus musculus )

    These mice are from Chen Dong.

  • Rictor floxed mice ( Mus musculus )

  • SLP-76 Y112/128F ( Mus musculus )

    These mice contain a mutation in SLP-76.

  • SLP-76 Y145F ( Mus musculus )

    These mice contain a mutation in SLP-76.


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Last updated: 2016-03-01T17:37:15.696-05:00

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