Immunology Graduate Group
Janis K. Burkhardt, Ph.D.
Associate Professor, Department of Pathology and Laboratory Medicine
Division of Cell Pathology
Children's Hospital of Philadelphia
Address: 816D Abramson Research Center
3615 Civic Center Boulevard
Philadelphia, PA 19104
Office Phone: (267) 426-5410
Lab Phone: (267) 426-5523
Fax: (267) 426-5165
Email: Jburkhar@mail.med.upenn.edu
Education:
Ph.D., Duke University
B.A., Washington University in St. Louis
Research Interests
Regulation and function of the T cell cytoskeleton
Research Summary
The focus of my lab is on the role of the cytoskeleton in T 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 membrane domain which is important for T cell signaling. One outcome of this signaling is the re-orientation of the microtubule array to face the bound target cell so that specialized secretory granules can then move along the microtubule scaffold toward the bound target. This polarized secretion ensures rapid destruction of the target and protection of healthy "bystander cells". Similar processes are important for directing T cell help. Our long-term goals in the lab are to understand how cell surface interactions trigger remodeling of the cytoskeleton, and how the cytoskeleton in turn affects T cell function. Proteins of current interest in the lab include Rho family members and WASP, the protein defective in the human immunodeficiency disorder Wiskott-Aldrich Syndrome. Another project involves members of the ezrin-radixin-moesin family, which we have found to be responsible for controlling the localization of important T cell signaling molecules.
Recent Publications
Allenspach, E.J., P. Cullinan, J. Tong, Q. Tang, A.G. Tesciuba, J.L. Cannon, S.M. Takahashi, R. Morgan, A.I. Sperling, and J.K. Burkhardt. 2001. ERM-dependent movement of CD43 defines a novel protein complex distal to the immunological synapse. Immunity 15:739-750.
Vyas, Y.M., K.M. Mehta, M. Morgan, H. Maniar, L. Butros, S. Jung, J.K. Burkhardt, and B. Dupont. 2001. Spatial organization of signal transduction molecules in the NK cell immune synapse during MHC class I-regulated noncytolytic and cytolytic interactions. J. Immunol. 167:4358-4367.
Morgan, M.M., C.M. Labno, G.A. Van Seventer, M.F. Denny, D.B. Straus and J.K. Burkhardt. 2001. Superantigen-induced T cell:B cell conjugation is mediated by LFA-1 and requires signaling through Lck but not ZAP-70. J. Immunol. 10:5708-5718.
Algeciras-Schimnich, A., L. Shen, B.C. Barnhart, A.E. Murmann, J.K. Burkhardt and M.E. Peter. 2002. Molecular ordering of the initial signaling events of CD95. Mol. Cell. Biol. 22:207-220.
Zeng, R., J.L. Cannon, R.T. Abraham, M. Way, D.D. Billadeau, J. Bubeck-Wardenberg, and J.K. Burkhardt. 2003. SLP-76 coordinates Nck-dependent WASP recruitment with Vav-1/Cdc42-dependent WASP activation at the T cell-APC contact site. J. Immunol. 171:136--1368.
Labno, C.M., C.M. Lewis, D. You, D.W. Leung, A. Takesano, N. Kamberos, A. Seth, L.D. Finkelstein, M.K. Rosen, P.L. Schwartzberg, and J.K. Burkhardt: Itk functions to control actin polymerization at the immune synapse through localized activation of Cdc42 and WASP. Current Biol. In Press.
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