Regulation of Apoptosis (Programmed Cell Death)

Earlier studies from this laboratory provided some of the first biochemical evidence that anticancer drugs induce apoptosis in susceptible cells, selective protein degradation occurs during this process, and intracellular cysteine proteases called caspases contribute to this degradation. Building on these earlier results, current studies are focused on understanding the pathways that lead to caspase activation and the mechanisms that regulate caspase activity. Part of these studies attempt to understand how phosphorylation of apoptotic pathway components alters their function and to identify the kinases responsible for this phosphorylation. A second group of studies, performed in collaboration with the laboratories of Gregory Gores and Viji Shridhar, is investigating the roles of the sulfhydryl protease cathepsin B and the serine protease HtRA1 in cell death processes. Additional projects involve examination of small molecule antagonists of antiapoptotic pathway components as potential modulators of chemotherapy-induced apoptosis.