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Srinivasa (Murty) Srinivasula, Ph.D.

Laboratory of Immune Cell Biology Investigator Building #37, Room #3016A 37 Convent drive Bethesda, MD 20892 Phone:   301-496-1648 Fax:   301-402-4844 E-Mail:   srinivsr@mail.nih.gov

Biography

Dr. Srinivasa Murty Srinivasula, received his Ph.D., in biochemistry-molecular biology at Banaras Hindu University, Varanasi, India and his post-doctoral training at Thomas Jefferson University, Philadelphia. His present research is focused on characterization of critical genes involved in cell death and survival. Dr. Srinivasula has been awarded the Special Fellow award by The Leukemia and Lymphoma Society and the Kimmel Scholar award by The Sidney Kimmel Foundation for Cancer Research.

Research

The interest of my research team is to understand the molecular pathways involved in various cellular processes like cell death (apoptosis) and survival. Apoptosis, or programmed cell death, is an evolutionarily conserved physiological process that plays an essential role in development and in homeostasis in all metazoans. Deregulation of apoptosis is linked to a number of pathological conditions like cancer, and immune and neurological disorders. The primary focus of our group is to characterize the proteins involved in regulation of apoptosis. A family of cysteine proteases, named caspases, plays critical role in apoptosis. Upon apoptotic stimuli, initiator procaspases (like procaspase-8 and -9) are activated by autocatalytic cleavage, and following this, they activate the effector caspases (like caspase-3, -6 and -7). Once activated these caspases cleave a number of cellular targets (like PARP, nuclear lamins, DFF/CAD etc.) and thus they disable important cellular processes. Interestingly, recent studies revealed that activation of caspases is also required for the execution of non- apoptotic cellular processes including hematopoietic cell proliferation and differentiation as well as cytokine processing during inflammation. Given the critical role of caspases both in apoptosis and in other cellular processes, it is crucial that their activation is tightly regulated. Recently it has been demonstrated that the caspase-9 inter-domain linker region binds XIAP, a member of the inhibitor of apoptosis protein family to negatively regulate caspase activity. One of the interests of my group is to study the mechanism of regulation of the caspases during apoptosis and cell proliferation and development by identifying novel caspase modulators.
Our research also focuses on the function and regulation of NF-kB. The members of nuclear factor (NF-kB) transcription factor family play central roles in various biological processes by regulating expression of genes involved in such diverse processes as inflammation, immune responses, differentiation, proliferation, and apoptosis. Our main focus is TNF-R1 internalization/endocytosis and the regulation or termination of IKK/NF-kB activation in response to upstream signaling by Tumor Necrosis Factor-a (TNF-a) and Interleukin-1 (IL-1).

This page was last updated on 6/12/2008.