My laboratory investigates the role of apoptotic dysfunction in tumor maintenance. Members of the BCL-2 family of proteins are critical adjudicators of death decisions. We are studying how interactions among anti-apoptotic members (including BCL-2, BCL-XL, MCL-1, BFL-1/A1, and BCL-w) and BH3-only pro-apoptotic members (including BID, BAD, BIM, BIK, PUMA, NOXA, BMF, and Hari-Kiri) can determine cancer cell survival. We are also investigating mimetics of BH3 domains derived from these proteins (including peptides and small molecules) as inhibitors of BCL-2 and the other anti-apoptotic proteins. We utilize a conditional transgenic mouse model of a BCL-2 dependent leukemia. We also study the mechanisms of mitochondrial dysfunction associated with apoptosis in normal and cancer cells. Our goal is to define the dependence of cancer cells on apoptotic dysfunction, and to target this dysfunction to specifically kill cancer cell.