Research
My research interests are aimed at studying cell biological processes in vivo, thereby understanding subcellular activity in the context of whole body physiology. In particular, my current research focuses on how the absorptive epithelial cells that line the intestine regulate the temporary storage and export of dietary fat.
Elevated levels of circulating fat in the blood are a known risk factor for cardiovascular disease. Following a meal, triglyceride-rich lipoproteins known as chylomicrons are produced by the intestine and contribute prominently to circulating triglyceride (TG) levels. The production of chylomicrons is primarily determined by the amount of fat ingested and absorbed. However, growing evidence suggests the intestine can actively regulate the rate of postprandial chylomicron production in part through transient TG storage and delayed export.
Intestinal enterocytes absorb and package dietary fatty acids into TG that is exported via chylomicrons or stored in cytoplasmic lipid droplets (LD). LDs are subcellular organelles composed of a core of TG and cholesterol esters surrounded by a monolayer of phospholipids and a variety of proteins, including perilipins. Intestinal LDs are dynamic storage compartments; they increase in number and size in the hours following a high-fat meal, but are nearly depleted 12–14 hours later in the absence of another meal. Despite the implications of intestinal LD regulation on postprandial serum TG levels, the mechanisms governing enterocyte LD regulation are poorly characterized.
My work aims to elucidate the cellular mechanisms that regulate the maintenance and turnover of intestinal LDs following a high-fat meal and how these mechanisms influence the production of chylomicrons. These studies capitalize on the powerful transgenic and in vivo imaging opportunities afforded by the zebrafish model vertebrate system.