233 S. 10th Street
Philadelphia, PA 19107
Microbiology and Immunology
Thomas Jefferson University
Research and Clinical Interests
My laboratory focuses on the function of proteins of the death-inducing signaling complex (DISC), including FADD, Caspase 8 and FLIP. FADD is critical for apoptosis induced by death receptors including TNF-R, Fas, and TRAIL-R. Death receptor induced apoptosis is essential for homeostasis in the immune system. Accumulating evidence indicates that death receptor signaling is essential for tumor surveillance/suppression. Mice lacking death receptors are predisposed to spontaneous and induced malignancy. However, FADD apparently has additional functions. FADD is not only required for apoptosis, but also play a role in lymphocyte proliferation which is essential for mounting immune responses to pathogens. Antigen-specific, TCR induced proliferation of T cells is defective in T cells. Our recent data revealed a novel function for FADD in Toll-like receptor (TLR) induced proliferation in B cells. Studies by others have suggested that FADD directly regulates replication of virus including VSV and flu virus. We have recently showed that mice lacking FADD specifically in T cells leads to immunodeficiency against LCMV and Lysteria monocytogenes. Similar effects were seen in Caspase 8 and FLIP deficient mice. Therefore, our system has direct relevance to cancer biology and vaccinology. We have expertise in signal transduction, lymphocyte responses in the context of innate and adaptive immunity. The emerging data in the regulation of virus/bacteria-induced responses by DISC proteins helped open a new area of study. There are ongoing collaborations between our laboratory and laboratories of Drs. Schnell, Eisenlohr, Dietzschold, Manser, and Alugupalli. Our research could be greatly facilitated by being a part of the JVC.