Since François Poulletier de la Salle observed solidified cholesterol from gallstones in 1769, cholesterol has been identified to play distinct roles in the maintenance of cell membranes and serves as a precursor for lipoproteins, steroid hormones, and bile acids. Curiously, cholesterol has also been found to regulate cell signaling.
Our lab focuses on membrane proteins in cholesterol biogenesis, transport, and signaling using multiple approaches from protein engineering, to x-ray crystallography and cryo-EM. To reveal the principle of cholesterol metabolism in cells, we are currently focusing on several membrane proteins that contain a Sterol-Sensing Domain (SSD) (e.g. Niemann-Pick C1, HMG-CoA reductase, Patched, and Dispatched). The SSD concept was proposed by the Brown and Goldstein Lab in 1996. Proteins with an SSD play indispensable roles in cholesterol metabolism and signal transduction.
We also are interested in the molecular mechanism of sterol-substrate recognition and delivery by membrane enzymes in the cholesterol biosynthetic pathway. Mutations in our proteins of interest can lead to serious health risks such as human inborn errors and cancers. Our research aims to increase our knowledge of these proteins in the cholesterol pathway to facilitate further development of treatments for related diseases.