Janis K. Burkhardt
Associate Professor, Dept of Pathology and Laboratory Medicine

Cell Biology and Physiology Program

Address

Children's Hospital of Philadelphia
816D Abramson Research Center (Office)
815 Abramson Research Center (Lab)
3615 Civic Center Boulevard
Philadelphia, PA 19104

Office tel.: 267 426-5410
Lab tel.: 267 426-5523
Fax: 267 426-5165
E-mail: Jburkhar@mail.med.upenn.edu


EDUCATION

Washington University in St. Louis: AB (Biology), 1983.

Duke University: PhD (Microbiology and Immunology), 1989.

Research Interest

• Regulation and function of the T cell cytoskeleton.

Key Words: T cell, cytoskeleton, actin, microtubules, WASP, ezrin, signal transduction, immune synapse.

Search PubMed for articles

Description of Research

The focus of our 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, facilitating the polarized secretion of lytic factors toward the appropriate target cell. 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. One major project addresses the regulation of actin at the “Immune Synapse” formed at the site of contact between a T cell and its target. This project is currently focussing on WASP and HS-1, two actin regulatory proteins linked to immunodeficiency and autoimmunity. Another project involves members of the ezrin-radixin-moesin family, which we have shown are key organizers of a novel protein complex distal to the site of target cell binding. We believe that this “distal pole complex” serves a sink for negative regulators of T cell activation, and are seeking to understand its molecular organization and function.

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.

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. 2003. Itk functions to control actin polymerization at the immune synapse through localized activation of Cdc42 and WASP. Current Biol. 13: 1619-1624.

Cannon, J.L., and J.K. Burkhardt. 2004. Differential roles for WASP in immune synapse formation and IL-2 production. J Immunol. 173:1658-62.

Gomez, T.S., M.J. Hamann, S. McCarney, D.N. Savoy, C.M. Lubking, M. P. Heldebrant, C.M. Labno, D.J. McKean, M.A. McNiven, J.K. Burkhardt, and D.D. Billadeau. 2005. The large GTPase Dynamin2 interacts with Vav1 and regulates T cell activation by controlling actin polymerization at the T cell – APC contact site. Nat Immunol 6:261-70.

Gomez T. S., McCarney, S.D., Carrizosa, E., Labno C., Comiskey, E. O., Nolz, J.C., Zhu, P., Rawlings, D.J., Freedman, B., Clark, M.R., Billadeau, D.D., and Burkhardt, J.K. HS1 functions as an essential actin-regulatory adapter protein at the Immunological Synapse. Immunity. 24: 741-52.

Lab

Rotation Projects

Several rotation projects are available. Topics could include analyzing regulation of HS1-dependent actin dynamics, analyzing the role of HS1 in protein trafficking and antigen presentation, or testing the role of cell polarity proteins such as Dlg1 in forming the distal pole complex and controlling T cell migration.

Lab personnel:

Esteban Carrizosa, Graduate Student
Meredith Hilton, Graduate Student
Ann Huang, Research Associate
Shuixing Li, Research Associate
Renell Morgan, Research Technician
Erin Comiskey, Research Technician