TORS Investigators – Team 2

Molecular Biology of Energy Metabolism

Lead Investigator

David J. Mangelsdorf, Ph.D., is a member of the U.S. National Academy of Sciences (2008), a Howard Hughes Medical Institute Investigator, and Chair of Pharmacology. He discovered the function of the nuclear receptor LXR and its role in bile acid and lipid metabolism. He is the recipient of the Heinrich Wieland Prize, First Umesono Memorial Award, and Adolf Windaus Prize for Bile Acid Research.

Associate Investigators

Michael S. Brown, M.D., is a Nobel Laureate (1985) who discovered the LDL receptor in collaboration with Joseph L. Goldstein, and who also identified SREBPs, which are transcription factors that regulate cholesterol and fatty acid biosynthesis. Brown and Goldstein produced a mouse model of lipodystrophy with features of the metabolic syndrome and showed that leptin treatment reversed the metabolic abnormalities in these mice. Dr. Brown is a member of the U.S. National Academy of Sciences (1980), and a recipient of the U.S. National Medal of Science (1988) and the Albany Medical Prize (2003).

Joseph L. Goldstein, M.D., was awarded the Nobel Prize (1985) together with Michael S. Brown for the discovery of the LDL receptor and for characterizing the central role of the receptor in cholesterol metabolism. More recently, he and Dr. Brown defined two transcription factors that regulate many aspects of lipid metabolism. They have produced numerous lines of genetically modified mice with defects in lipid metabolism. Dr. Goldstein is a member of the U.S. National Academy of Sciences (1980), and a recipient of the U.S. National Medal of Science (1988) and the Albany Medical Prize (2003).

Jay D. Horton, M.D., is a gastroenterologist and Pew Scholar whose research focuses on molecular mediators of fatty liver and lipid metabolism. He demonstrated that the transcription factor SREBP-1c plays a major role in regulating hepatic lipid metabolism in response to insulin. Dr. Horton has specialized expertise in the development and characterization of mouse models of obesity and insulin resistance.

Steven A. Kliewer, Ph.D., formerly the Director of Nuclear Receptor Biology at GlaxoSmithKline, is now Professor of Molecular Biology at UT Southwestern. He discovered that thiazolidinediones are ligands for PPAR and the functions of the PXR and CAR receptors in xenobiotic metabolism.

Joyce Repa, Ph.D., is an Associate Professor of Physiology who has performed seminal studies in the nuclear receptor field. She is currently studying receptor function in the liver, intestine, and pancreas.

Philipp Scherer, Ph.D., is Director of the Touchstone Center for Diabetes Research. He has led research showing in mice how an abundance of adiponectin, a hormone that controls sensitivity to insulin, and a lack of leptin, a hormone that curbs appetite, spurs storage of excess calories in fat tissue instead of in liver, heart, or muscle tissue — places where excess fat can lead to inflammation, diabetes, and heart disease.

Kosaku Uyeda, Ph.D., is a Professor of Biochemistry who discovered ChREBP, a transcription factor that mediates glucose-induced lipogenesis in the liver.