Our research program focuses on three specific areas relating cholesterol metabolism with individual susceptibility for coronary heart disease. Particular emphasis is placed on the genetic factors that are important for regulation of cholesterol transport and in the maintenance of cell functions in the arterial wall. One area of research uses induced mutant mice (transgenic and knockout mice) to determine the role of lipolytic enzymes and intestinal cell surface transporters in mediating dietary fat and cholesterol absorption through the gastrointestinal tract. Mutant mice generated from these studies are also being used as an animal model to explore the potential of gene therapy as treatment for nutrient alabsorption due to pancreatic insufficiency. The mechanism by which the lipolytic enzymes and transport proteins mediates cholesterol absorption is being explored using protein chemistry and site specific mutagenesis approaches.