Why study lysosome biology?

Lysosomes are degradative organelles present in all eukaryotic cell types and perform multiple critical functions in addition to their role as an ‘incinerator’ in the cell. Lysosomes are the epicenter of all trafficking pathways and integrate cellular metabolism to permit critical decisions on life and death, and growth or quiescence. They are critically important organelles as evidenced by genetic inborn errors collectively term ‘lysosome storage diseases’; which result from deficiency of structural or enzymatic proteins in the lysosomes and trigger global lysosome dysfunction. These disease affect the central nervous system and/or the heart in every single instance indicating how critical lysosome function is these differentiated primary cell types. My lab’s primary interest is to define the role of lysosomes in cellular homeostasis and response to stress. Work from our lab and others has uncovered evidence for acquired lysosome dysfunction in cardiovascular, metabolic and neurodegenerative diseases. We have shown that acquired lysosome dysfunction is a major contributor to cardiac myocyte loss in myocardial ischemia-reperfusion injury and in cardiomyopathy and heart failure. 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. Remarkably, all these diseases are predisposed to by a common set of risk factors. For example, aging is a common risk factor for all these diseases and has been implicated in causing progressive lysosome dysfunction. As the PI or co-investigator on studies funded through National funding mechanisms, we have developed the expertise and tools to experimentally perturb and evaluate lysosome biology, concomitantly with disease modeling in in vitro and in vivo systems. Our goal is to understand the mechanisms for acquired lysosome dysfunction in human diseases, assess the efficacy and safety of therapeutically targeting lysosome biogenesis and function in animal models and develop therapies that can be translated to humans to treat diseases characterized by acquired lysosome dysfunction.

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