Assistant Professor of Medicine Department of Medicine Division of Endocrinology, Metabolism, and Clinical Nutrition Investigative Interests: Study the molecular role of cholesterol in development by the use of knockout and transgenic strategies; lipid raft proteomics on cholesterol biosynthesis disorders. Primary Focus: The primary focus of my research program has been on the role of mouse cholesterol biosynthesis on embryonic development. The long-term goal for this program is to understand the molecular role of cholesterol in embryogenesis. Genetic defects in enzymes responsible for post-squalene cholesterol biosynthesis have recently emerged as important causes of congenital dysmorphology syndromes. If the enzymes responsible for post-squalene cholesterol biosynthesis is genetically deleted from mice, embryonic formation fails completely, causing neonatal lethality. We are currently addressing the role of cholesterol deficiency caused by Dhcr7 and Dhcr24 ablations in abnormal embryogenesis using a combination of knockout and transgenic strategies. To elucidate the pathogenesis of developmental abnormalities and lethal effects caused by abrogation of endogenous cholesterol biosynthesis, we have engineered mice that selectively express human DHCR7 protein in brain, lung or liver from transgenes driven by tissue-specific promoters, respectively. These transgene-containing mice will then be bred to Dhcr7-/- background to generate animals that express human DHCR7 protein in tissue-specific patterns. Primary results have indicated that CNS defects, involving abnormal myelination and neurogenesis, contributes significantly to the early postnatal lethality of Dhcr7-/- mice and may be important in the severity of SLOS in humans.