Three members of the SREBP family have been described. One of these, SREBP-1c, is activated at the transcriptional level by insulin. When animals ingest excess energy in the form of carbohydrate or protein, the pancreas is stimulated to secrete insulin into the portal vein. The insulin reaches the liver where it activates transcription of the SREBP-1c gene. The resultant membrane-bound SREBP-1c protein is processed proteolytically into its nuclear form, and it activates genes that cause the excess energy to be stored in the form of fatty acids and triglycerides.

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 currently 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.