A major focus of our laboratory is to understand hepatic lipid droplets. Over 1.5 billion people worldwide have non-alcoholic fatty liver disease (NAFLD), which is characterized by the accumulation of lipid droplets. NAFLD greatly increases the risk of more advanced liver diseases (e.g. steatohepatitis, hepatocellular carcninoma) as well as metabolic diseases (e.g. Type 2 Diabetes, cardiovascular diseases, etc.), thus, understanding its underlying etiology is critical. Specifically, we ask the following questions:
What are lipid droplets comprised of?
Once thought of as inert forms of energy storage, lipid droplets are now recognized to be dynamic organelles with unique lipid and protein composition. We are particularly interested in identifying and characterizing the role of specific resident proteins as mediators of lipid droplet metabolism and signaling.
What regulates lipid droplet turnover?
These studies characterize lipases and related proteins and processes (i.e. lipophagy) that influence lipid droplet catabolism. We want to know how these proteins are regulated and what factors contribute to lipid droplet breakdown.
How do lipid droplets communicate to the rest of the cell?
Lipid droplets represent the major storage form of energy in most cells. Much as adipose tissue communicates to the rest of the body, lipid droplets must communicate intracellularly to influence cell function. Our laboratory is interested in elucidating signal networks that link lipid droplet catabolism to cell function. We have recently identified a novel signaling pathways linking ATGL-catalzyed lipolysis to SIRT1 activation. Ongoing studies are further defining this signaling pathway and its physiological ramifications.
How do lipid droplets link NAFLD to its comorbidities?
What is it about lipid droplets that cause disease development or progression? Similar to the above, we want to know how alterations in lipid droplet composition or turnover influence disease development. For example, why does NAFLD track closely with hepatic insulin resistance? We believe that lipid droplet metabolism is a key node that regulates insulin signaling and hepatic glucose production. Although a main focus is in the liver, we are also pursuing other studies linking lipid droplets to metabolic disease including cancer as well as the role of lipid droplets in the aging process.
Although most of our studies focus on the liver, we have also become very interested in understanding lipid droplet biology and energy metabolism in the muscle as well. Numerous ongoing studies are involved with muscle lipid metabolism in the context of exercise and/or insulin resistance in both animals and humans.