WASHINGTON UNIVERSITY MEDICAL CENTER, Saint Louis (United States of America)
The Diwan lab's primary research interest is to define the role of lysosomes in cellular homeostasis and response to stress. We are actively interrogating lysosome biology in multiple cell types and disease states including heart failure, Alzheimer’s pathogenesis, and diabetes. The lab has uncovered evidence for acquired lysosome dysfunction as a major contributor to cardiac myocyte loss in myocardial ischemia-reperfusion injury and cardiomyopathy. We have also demonstrated that stimulating lysosome function by intermittent fasting and activation of TFEB to stimulate lysosome biogenesis preconditions the myocardium to ischemia-reperfusion injury and ameliorates proteotoxic cardiomyopathy. Our work has revealed that mitophagy is impaired in oocytes in mice fed an obesogenic diet, which induces transgenerational transmission of mitochondrial abnormalities in hearts of offspring. We aim to develop therapeutic strategies for stimulating lysosome function to prevent heart failure.