Mechanisms of Inter-organelle Communication
How do our cells metabolize the nutrients we receive from our diet and share essential metabolites like cholesterol among their different organelles? My lab is interested in inter-organelle communication as an organizational principle in cell metabolism. As complicated molecular machines, our cells must constantly digest ‘old’ lipids and synthesize ‘new’ ones to persist. This requires elaborate systems for sensing metabolic stress and demand, as well as trafficking pathways that move lipids from one organelle to another.
Recent work suggests that inter-organelle Membrane Contact Sites (MCSs)—specific regions where organelles physically touch within cells””serve as super-highways for lipid flux, as well as hubs for metabolic decision-making. My lab is focused on understanding how MCSs form, how they are regulated, and how the cell uses them for the exchange of lipids and other metabolites. In particular, we seek to understand how lysosomes, the “garbage bags” where cellular biomolecules are digested, exchange nutrients with other organelles like the Endoplasmic Reticulum that synthesizes most cellular lipids. Understanding this inter-organelle cross-talk is essential in the therapeutic treatment of metabolic syndromes such as obesity and diabetes, as well as the cellular basis for aging. Numerous genetic diseases such as Niemann Pick arise from the aberrant accumulation of metabolites such as cholesterol and sphingolipids in lysosomes. My lab is thus interested in understanding how lysosomes rid themselves of the wastes they generate, and how cells 'recycle' these wastes into new lipids and proteins via inter-organelle metabolic flux.
To study inter-organelle communication, my lab utilizes cell biology, biochemistry, genetics, and structural biology. We also utilize numerous model systems including budding yeast, Drosophila melanogaster, human tissue culture, and bacteria.