At least a dozen individual “programs” mediate cell death, but how these interconnect to produce an integrated cell death response is poorly understood. Caspase-9 is the canonical initiator protease in the mitochondrial apoptosis pathway. This project builds on the novel finding that caspase-9 also plays a critical role in a second important cell death program, mitochondrial-dependent necrosis.

Richard Kitsis, M.D., has received a four-year, $2.5 million National Institutes of Health grant to delineate the molecular mechanism by which caspase-9 mediates necrosis. Further, the project explores why caspase-9 seems to play a pivotal role in heart damage during myocardial infarction (“heart attack”), a situation in which at least 6 cell death programs are activated, raising the possibility that caspase-9 could provide a novel therapeutic target for this common and deadly syndrome.

Dr. Kitsis is professor of medicine, of cell biology, the Dr. Gerald and Myra Dorros Chair in Cardiovascular Disease, director of the Wilf Family Cardiovascular Research Institute at Einstein, and a cardiologist at Montefiore Health System. (1R01HL164772-01)