Our laboratory discovered the SREBPs and described their unique transport-dependent proteolytic activation. We then discovered SCAP the two proteases that process SREBPs, and the role of Insigs as ER retention proteins. We are exploring the molecular mechanisms by which cholesterol, fatty acids, and insulin control this process. We use experimental systems ranging from protein crystallography to cell biology to animal physiology. Over the years we have trained more than 20 graduate students and 100 postdoctoral fellows, all of whom are pursuing productive careers in biomedical research.