Janis K. Burkhardt, Ph.D.
Children's Hospital of Philadelphia
Perelman School of Medicine University of Pennsylvania
816D Abramson Research Center
3615 Civic Center Blvd.
Philadelphia, PA 19104
Fax: (267) 426-5165
Lab: (267) 426-5523
A.B. (Biology, Magna Cum Laude)
Washington University, 1983.
Ph.D. (Microbiology and Immunology)
Duke University, 1989.
Description of Research ExpertiseResearch Interests
Regulation of cytoskeletal dynamics in T cells and dendritic cells, and cytoskeletal control of the immune response
Keywords: T cells, dendritic cells, signaling, cell migration, antigen presentation, cytoskeletal dynamics, protein traffic, immunodeficiency, autoimmunity, vaccine development, cancer immunotherapy, integrins
The focus of my 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 is important for T cell signaling events leading to lysis of the tumor cell. Similar processes are important for directing and modulating T cell help. In dendritic cells, actin regulatory proteins control the uptake and presentation of antigens, migration of antigen-bearing cells from sites of infection to lymphoid organs, and defining the outcome of T cell stimulation. Our long-term goals in the lab are to understand how receptor-ligand interactions at the cell surface trigger remodeling of the cytoskeleton, and how the cytoskeleton in turn affects the immune response. Proteins of current interest in the lab include WASP, an actin regulatory protein involved in immunodeficiency disease, HS1, a related protein implicated in autoimmune disease, and Crk family adapter proteins, proteins that control T cell adhesion and migration.
Possible rotation projects are always changing. Topics could include analyzing regulation of T cell actin dynamics at the immunological synapse, analyzing actin function during antigen presentation in dendritic cells, or manipulating cytoskeletal signaling pathways to modify T cell migration during T cell immunotherapy.
Nathan Roy, Postdoctoral Fellow
Shuixing Li, Research Associate
Edward Williamson, Research Associate
Vidhi Chandra, Research Technician
Selected PublicationsShaffer MH, Dupree RS, Zhu P, Saotome I, Schmidt RF, McClatchey AI, Freedman BD, Burkhardt JK.: Ezrin and moesin function together to promote T cell activation. J Immunol 182(2): 1021-1032. Jan 2009 PMCID: PMC3491660.
Huang Y, Comiskey EO, Dupree RS, Li S, Koleske AJ, Burkhardt JK.: The c-Abl tyrosine kinase regulates actin remodeling at the immune synapse. Blood 112(1): 111-119. Jul 2008 PMCID: PMC2435682.
Burkhardt, J.K., Carrizosa, E. and Shaffer, M.H.: The actin cytoskeleton in T cell activation. Ann Rev Immunol 26, 233-259, Nov 2008.
Nolz JC, Gomez TS, Zhu P, Li S, Medeiros RB, Shimizu Y, Burkhardt, JK, Freeman BD, Billadeau, DD. : WAVE2 regulates actin cytoskeletal reorganization and CRAC-mediated calcium entry during T cell activation. Current Biology 16(1): 24-34, Jan 2006.
Gomez TS, McCarney SD, Carrizosa E, Labno CM, Comiskey EO, Nolz JC, Zhu P, Freedman BD, Clark MR, Rawlings DJ, Billadeau DD, Burkhardt, JK. : HS1 functions as an essential actin-regulatory adapter protein at the immune synapse. Immunity 24(6): 741-752, Jun 2006.
Gomez TS., Hamann MJ., McCarney S., Savoy DN., Lubking CM., Heldebrant MP., Labno CM., McKean DJ., McNiven MA., Burkhardt JK., Billadeau DD.: Dynamin 2 regulates T cell activation by controlling actin polymerization at the immunological synapse. Nature Immunology 6(3): 261-270, Mar 2005.
Labno CM., Lewis CM., You D., Leung DW., Takesono A., Kamberos N., Seth A., Finkelstein LD., Rosen MK., Schwartzberg PL., Burkhardt JK.: Itk functions to control actin polymerization at the immune synapse through localized activation of Cdc42 and WASP. Current Biology 13(18): 1619-1624, Sept 2003.
Allenspach EJ, Cullinan P, Tong J, Tang Q, Tesciuba AG, Cannon JL, Takahashi SM, Morgan R, Burkhardt JK, Sperling AI.: ERM-dependent movement of CD43 defines a novel protein complex distal to the immunological synapse. Immunity 15(5): 739-750, Nov 2001.
Cannon JL, Labno CM, Bosco G, Seth A, McGavin MH, Siminovitch KA, Rosen MK, Burkhardt JK.: Wasp recruitment to the T cell:APC contact site occurs independently of Cdc42 activation. Immunity 15(2): 249-259, Aug 2001.
Billadeau, D.D. and Burkhardt, J.K.: Regulation of Cytoskeletal Dynamics at the Immune Synapse: New Stars Join the Actin Troupe. Traffic 7(11): 1451-1460. Nov 2006.