My laboratory takes a multi-pronged approach to identifying and characterizing novel genes involved in lipid and glucose metabolism. Starting with unbiased, forward genetic screens in zebrafish, we isolate mutants with lipid phenotypes of interested (e.g., inappropriate accumulation of lipids in the liver, altered adipose lipid mass). We then clone and characterize the affected genes. We also use modern genetic methods to delete or selectively express genes of therapeutic interest, with a particular emphasis on the control of intestinal lipid handling as a platform for treating dyslipidemia and atherosclerosis. We take similar approaches to elucidating the roles of gene identified in human population genetics studies in glucose metabolism and type 2 diabetes mellitus pathogenesis. Characterization of mutant and transgenic zebrafish involves a broad range of methods spanning sophisticated microscopy (confocal and transmission electron), biochemical techniques, and, where appropriate, pilot pharmacological studies. We use in vitro enzymology, cell culture (including primary culture of human hepatocytes), and rodent (mice and rats) physiology to complement our work in zebrafish.