Hongyuan Yang

The primary goal of my laboratory is to understand the molecular mechanisms governing the sorting, trafficking, and storage of cellular lipids in health and disease. A major direction has been to define how lipid droplets originate and grow from the endoplasmic reticulum. Lipid droplets store triacylglycerols and cholesteryl esters and play important roles in cell biology and physiology. However, the mechanisms governing their biogenesis and growth remain incompletely understood. My group identified several key proteins that regulate lipid droplet formation, including seipin, AGPAT2, ORP5 and DFCP1 etc. Seipin has now become one of the most relevant protein to the biogenesis of lipid droplets. Importantly, both seipin and AGPAT2 are essential to adipogenesis, as null mutations in the seipin or AGPAT2 gene cause severe congenital generalized lipodystrophy in humans. Thus, the biogenesis of lipid droplets in a cell is intimately linked to the formation and maintenance of adipose tissue. An ongoing effort in my laboratory is to elucidate the molecular mechanisms underlying lipid droplet formation and to understand how lipid droplet formation may impact the structure and function of adipose tissue. Our work in this area has generated new insights into the storage of lipids at both cellular and systemic levels. Another major direction has been to investigate how lipids are sorted and transported in mammalian cells. Lipid distribution is highly uneven among organellar membranes. How mammalian cells maintain distinct lipid composition for each organellar membrane remains a fundamental question in biology. My group identified ORP2 as a key protein that delivers cholesterol to the plasma membrane where most cellular cholesterol resides. My group also identified TMEM41B and VMP1 as novel scramblases of the endoplasmic reticulum. Our work along this direction has generated new insights into how cells regulate the distribution of key lipids such as cholesterol and phosphatidylserine. Our current effort focuses on the physiological and pathological consequences of dysregulated lipid distribution. Overall, our work has important implications for obesity, diabetes, cancer, cardiovascular and neurogenerative diseases. Based on original discoveries made by our group, new compounds which may be used to treat cancer and neurodegenerative disorders are being developed.