The long-term goal of our laboratory is to understand the pathways and biochemical mechanisms controlling the activation and execution of apoptosis in mammalian cells.
Apoptosis is a biochemically and morphologically distinct form of programmed cell death.
Initiated by a variety of intercellular and intracellular signals, apoptosis is executed through an intrinsic cellular suicide program that results in early DNA fragmentation accompanied by nuclear and cytoplasmic condensation. Apoptosis is believed to play an essential role in development, tissue homeostasis, defense against viral infection, and clearance of damaged cells in multicellular organisms. Inappropriate activation or suppression of apoptosis are associated with the pathogenesis of some of the most devastating human diseases, such as cancer, neurodegenerative disease, auto-immune disease, AIDS, and ischemic stroke. We have been focusing our research efforts on the dissection of two of the best characterized biochemical events during apoptosis, namely the activation of Caspase 3 protease and fragmentation of DNA into nucleosomal fragments. We have set up in vitro systems that duplicate these two events and fractionated cytosol from large scale cultured HeLa cells to identify and purify the individual protein factors contributing to Caspase 3 activation and the DNA fragmentation reaction.