Grant: Project Grant

Cholesterol is one of the most important biological molecules in determining cell membrane structure, and the synthesis of steroid hormones, bile acids, and vitamin D. Cholesterol plays a role in many metabolic syndromes (e.g. obesity, insulin resistance, and hypertension); and most importantly it is a high risk factor for cardiovascular disease. The key enzymes in cholesterol synthesis are located in the endoplasmic reticulum, a membrane system responsible for the control and regulation of calcium homeostasis. We discovered a direct link between calcium and cholesterol biology. Modulation of cellular calcium content directly influences cholesterol distribution in cells and consequently regulation of cholesterol abundance on the body. We propose to dissect the molecular machinery responsible for the calcium-dependent effects on cholesterol in the cells. We plan to develop calcium-dependent strategies to control cholesterol metabolism in the cells. These strategies would then be useful to positively impact cholesterol related human disease including cardiovascular conditions.