I am investigating how cells sense nutrients in their internal and external environment, and how they translate nutrient availability into metabolic programs for growth, differentiation, or quiescence. In particular, my laboratory explores how lysosomes, organelles previously thought of as cellular “recycle bins,” operate as metabolic “command and control” centers that signal nutrient availability to the master growth regulator, mTORC1 kinase, and enable critical repair processes that maintain cell viability and function over time. To explore these exciting directions, we are developing novel techniques to probe organelle function both in vivo and in vitro and integrate them with advanced live cell microscopy and high throughput approaches. Our studies are uncovering previously unknown functions of the lysosome and could lead to novel therapeutics for diseases driven by aberrant lysosomal function, including cancer and neurodegenerative disease.
As an Innovation Fund investigator, Zoncu is teaming up with the lab of Shingo Kajimura, Ph.D., to explore the molecular basis of interorganelle communication and energy maintenance. Adipose tissue is a dynamic organ that can interconvert between energy-storing white adipocytes and energy-burning beige adipocytes in response to nutrition and thermal stress. This process involves shifting mitochondria content in a cell, yet little is known about the signals that control the synthesis or breakdown of the organelle in response to changing cellular conditions. Combining their expertise in organelle and metabolism biology and using high throughput screens in a genetically engineered adipocyte model, the pair will illuminate how communication between mitochondria and lysosome drives adipocyte remodeling and energy homeostasis. This project will provide a unique opportunity to identify potential factors involved in metabolic disorders such as obesity and diabetes, as well as further our understanding of the roles of cellular organelles in health and disease.