- Professor of Medicine, Center for Cardiovascular Research
- Charlie W. Shaeffer, MD Distinguished Professor of Medicine.
Lysosome biology in cellular stress and homeostasis.
Role of lysosomal pathways in cardiac pathophysiology
Our lab is investigating the regulation of lysosome function in cardiac physiology and pathology. Our work indicates that lysosomal pathways are impaired in ischemia-reperfusion injury, due to impaired autophagosome-lysosome fusion and transcriptional suppression of the autophagy-lysosome machinery, resulting in cardiomyocyte death. Ongoing studies are focused upon identifying the molecular mechanisms of transcriptional regulation of the lysosomal degradative machinery. Our goal is to identify and modulate signaling pathways that facilitate removal of damaged organelles and establish restorative organelle biogenesis, under stress, to enhance cardiomyocyte survival. In particular, we are focused upon developing strategies to translate the benefits of calorie restriction to cardioprotection, via its effects on the lysosome machinery. We are also studying the molecular and cellular mechanisms that link lysosome dysfunction to development of hypertrophic cardiomyopathy in Danon disease, which results from loss of lysosomal membrane protein, LAMP2.
Enhancing lysosome biogenesis to treat diabetes and amyloid pathology
In collaboration with investigators in cardiology and endocrinology, we are studying the role of lysosome dysfunction in pancreatic beta cells; and developing strategies to enhance cell survival under metabolic stress. In collaborative studies with neurologists, we are investigating the cell biology of the effects of stimulating lysosome biogenesis in various cell types to counter amyloid plaque pathogenesis, and prevent and/or treat Alzheimer’s Disease.
Phone: 314-747-3457 (Office) | 314-362-1984 (Lab)