Lipid droplets are dynamic neutral lipid (i.e. fat and sterol esters) storage organelles that function as hubs of lipid metabolism, providing an “on demand” source of fatty acids that can be used for energy, membrane biogenesis, and lipid signaling pathways. Lipid droplets are formed at the endoplasmic reticulum (ER) in a process involving the deposition of neutral lipids between the leaflets of the ER, followed by the emergence of the lipid droplet into the cytoplasm from the outer leaflet. The mature lipid droplet can be degraded by lipolysis or through a selective autophagic pathway known as lipophagy. How these pathways are regulated under different conditions and in different cell types remain to be determined. Furthermore, alterations in lipid droplet abundance are associated with a wide variety of diseases. Indeed, the accumulation of large hepatic lipid droplets is the pathological hallmark of fatty liver disease. Interestingly, mutations in certain genes (e.g. TM6SF2 and PNPLA3) are associated with increased risk of fatty liver.

    Our research aims to understand the mechanisms that regulate the biogenesis of lipid droplets and their functions in health and disease. For example, we discovered roles for lipid droplets in the prevent of lipotoxic damage to mitochondria (Dev Cell, 2017), developed chemoproteomic methods to study lipid droplet proteome remodeling (Dev Cell, 2018), and applied CRISPR screens to reveal new regulators of lipid droplet dynamics (bioRxiv, 2022). Some major questions include: How do lipid droplets form? How is the lipid and protein composition controlled? How are stored triacylglycerol molecules protected from oxidative damage? What are the functions of lipid droplets and how are these altered in diseases such as non-alcoholic fatty liver disease?