Washington University in St. Louis (WU)
My research focuses on the mechanisms of programmed cell death in the heart, which plays a central role in causing heart failure in response to ischemic injury and pressure overload hypertrophy. We have previously characterized the role of two stress induced cell death initiators, Bnip3 and Nix, which are pro-death members of the Bcl2 family of apoptosis regulators, and are induced by cardiac ischemic injury and pressure overload on the heart such as in hypertension, respectively. Bnip3 and Nix target to and permeabilize mitochondria leading to programmed cardiomocyte death. Recently, we have found Bnip3 expression induces autophagy in the mouse heart, which contributes to adverse left ventricular remodeling, due to impaired autophagic flux. We have become interested in defining the role of impaired autophagic flux in cardiomyocyte death. Impaired autophagosome-lysosome fusion and accumulation of autophagic vacuoles is the hallmark of Danon disease, a condition characterized by hypertrophic cardiomyopathy, and caused by mutations in Lamp2 gene, which leads to loss of functional LAMP2 protein. We are characterizing the role of LAMP2 in autophagosome-lysosome fusion and autophagic flux, as a determinant of cardiomyocyte viability in normal cardiac physiology and in response to ischemia-reperfusion injury.