David Mangelsdorf is Professor and Chair of the Department of Pharmacology at the University of Texas Southwestern Medical Centers and an Investigator of the Howard Hughes Medical Institute. Mangelsdorf holds the Alfred G. Gilman Distinguished Chair in Pharmacology and the Raymond and Ellen Willie Distinguished Chair in Molecular Neuropharmacology. Mangelsdorf received his B.S. in Biology and Chemistry from Northern Arizona University in Flagstaff and his Ph.D. in Biochemistry from the University of Arizona in Tucson. He received his postdoctoral training at The Salk Institute for Biological Studies with Ronald Evans at the Salk Institute, where he discovered the orphan nuclear receptor RXR and its ligand, 9-cis retinoic acid. Mangelsdorf has since characterized ligands and physiologic functions for several mammalian orphan receptors, including the oxysterol receptors (LXRs), the bile acid receptor (FXR), and the dafachronic acid receptor (DAF-12) that is found in nematodes and governs the dauer diapause. He has received several honors including the John J. Abel Award in Pharmacology, the Adolf Windaus Prize for Bile Acid Research, the Heinrich-Wieland-Preis in Lipid Research, the Endocrine Society’s Gerald D. Aurbach Award, the Karolinska Institute’s Rolf Luft Award in Endocrinology and Diabetes, and he is a member of the National Academy of Sciences.

Research Interests

Dr. Mangelsdorf runs a joint laboratory with his long-time collaborator, Dr. Steven Kliewer. Their lab has discovered several therapeutic targets that are being developed to treat diverse diseases such as cholestasis, obesity, diabetes, fatty liver disease, pancreatitis and nematode parasitism. Current research focuses on understanding the molecular and physiologic components of two endocrine factors, FGF19 and FGF21, which respectively play distinct roles in enterohepatic control of bile acid physiology and neuroendocrine control of nutrient stresses, such as starvation, unbalanced macronutrient diets, and alcohol. Following their discovery of the hormonal ligands and signaling pathway for the C. elegans nuclear receptor, DAF-12, they have shown this pathway is conserved in parasitic nematodes and is the key step in governing parasite infection. Their current research is directed at investigating the therapeutic potential of targeting this pathway.

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Section 42: Medical Physiology and Metabolism