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 cells, cytoskeleton, actin, dendritic cells, microtubules, WASP, ezrin, signal transduction, immune synapse.

Description of Research

The focus of our 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 promotes T cell signaling. One outcome of this signaling is the polarized secretion of lytic factors toward the 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 "Immunological Synapse" formed at the site of contact between a T cell and its target. We are currently focusing on WASP and HS1, two actin regulatory proteins linked to immunodeficiency and autoimmunity, and c-Abl an upstream kinase associated with certain leukemias. A second T cell 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. In a third project, we are studying the role of actin regulatory proteins in dendritic cells. In these "professional antigen presenting cells" we have found that HS1 and WASp are required for antigen uptake in peripheral tissues, and for migration of these cells into lymphoid organs, where they present these antigens to T cells.

Selected Publications

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

Gomez T. S., McCarney, S.D., Carrizosa, E., Labno C., Comiskey, E. O., Nolz, J.C., Zhu, P., Freedman, B.D., Clark, M.R., Rawlings, D.G., Billadeau, D.D., and Burkhardt, J.K. 2006. HS1 functions as an essential actin-regulatory adapter protein at the immune synapse. Immunity 6:742-51.

Huang Y., Comiskey EO., Dupree RS., Li S., Koleske AJ., Burkhardt JK. 2008. The c-Abl tyrosine kinase regulates actin remodeling at the immune synapse. Blood, 112:111-19.

Burkhardt, J.K., Carrizosa, E. and Shaffer, M.H. 2008. The actin cytoskeleton in T cell activation. Ann. Rev. Immunol. 26:233-59.

Search PubMed for more articles

Lab

Rotation Projects

Several rotation projects are available. Topics could include analyzing regulation of HS1-dependent actin dynamics in T cells, analyzing the role of HS1 in protein trafficking and antigen presentation in dendritic cells, or testing the role of ezrin and moesin in controlling T cell adhesion and migration

Lab personnel:

Esteban Carrizosa, Graduate Student
Meredith Shaffer, Graduate Student
Deborah Klos Dehring, Postdoctoral fellow
Ann Huang, Research Associate
Shuixing Li, Research Associate
Fiona Clarke, Research Technician