C.b. Srikant

Biography

Academic Degree: Ph. D. 1973, University of Madras, Madras, India Post-Doctoral Training: 1974-1978 (Dr. Roger Unger), Department of Internal Medicine, University of Texas Health Science Center and V.A. Hospital, Dallas, TX, U.S.A. Assistant Professor, 1982 Department of Medicine, McGill University Associate Professor, 1990, Department of Medicine, McGill University Professor, 2000- , Department of Medicine, McGill University

Research Interest

The focus of my research is the elucidation of the mechanisms of cytoprtoective effects of growth factors and somatostatin. Our findings have provided novel insights into the receptor subtype-specific antiproliferative action of somatostatin. It exerts cytotoxic action causing apoptosis in estrogen responsive breast cancer cells and in pituitary tumor cells. Its action is SHP-1-dependent and leads to induction of p53, Bax, an acidic endonuclease and decrease in intracellular pH. These actions are uniquely mediated by a single human somatostatin receptor subtype (hSSTR3). We showed also that somatostatin promotes hypophosphorylion of Rb leading to G1 cell cycle arrest via other hSSTRs (hSSTR5>2>4>1). These findings imply the potential therapeutic utility of SST analogs in oncology, but with varied outcome depending on the relative abundance of the SSTR, and the mediators of apoptosis and cell cycle in a given tumor. More recently, our work has centered on the Reg genes that promote pancreatic b-cell survival, growth and function. We have found that induced expression of murine Reg2 in mouse insulinoma cells induces the basal expression of the ER chaperone protein GRP78 and inhibits the detrimental unfolded protein response leading to apoptosis induced by glucolipotoxicity and chemical inducers of ER stress. These findings point to the beneficial effect of induced expression of Reg in protecting islet cells against glucolipotoxic stress encountered in type 2 diabetes and obesity.