Our lab’s primary interest is to define the role of lysosomes in cellular homeostasis and response to stress. Dr. Diwan’s training as a cardiologist led him to focus on the role of lysosome function in cardiac myocyte death, which plays a central role in causing heart failure in response to myocardial infarction and pressure overload hypertrophy. Our lab has uncovered evidence for dysregulation of the lysosome machinery as a major contributor to cardiac myocyte loss in myocardial ischemia-reperfusion injury. Our work has also extended these findings to uncover evidence for lysosome dysfunction in various CNS cell types in Alzheimer’s disease and in pancreatic beta cells in obesity-induced diabetes, underscoring the importance of acquired lysosome dysfunction in triggering multiple chronic diseases that are predisposed by common risk factors. As the PI or co-investigator on studies funded through National funding mechanisms, Dr. Diwan and the group have developed the expertise and tools to experimentally perturb and evaluate lysosome biology, concomitantly with disease modeling in in vitro and in vivo systems.
Area of focus in the Diwan Lab: Our focus is to understand the role of lysosome function in common cardiometabolic diseases and Alzheimer’s disease, and whether acquired lysosome dysfunction is a common cellular defect that underpins predisposition to these diseases that often affect the same individuals that are predisposed to them based upon a common set of risk factors. We are also interested in understanding how lysosome function in oocytes regulates epigenetic reprogramming of genomic and mitochondrial DNA as a contributor to cardiovascular risk in the offspring. Lastly, we are focused upon discovering novel regulators of lysosome biogenesis in simple model systems. These areas of focus are broadly divided into:
Studies in the Cardiovascular System
Discovery Studies to Identify Novel Regulators of Lysosome Biogenesis in C. elegans
Studies in Alzheimer’s disease pathogenesis
Studies in diabetes pathogenesis
Overall, our laboratory is focused upon understanding the regulation of the lysosome machinery in homeostasis and disease states, and to develop strategies to target it for therapeutic benefit. In ongoing collaborations, we have begun to test small molecule activators of the lysosome biogenesis pathway in cardiomyopathies and diabetes to determine their efficacy and safety. These studies are the first step before large animal studies, and eventual translation into human clinical trials.