David Mangelsdorf, Ph.D. Professor & Chair Endowed Title Alfred G. Gilman Distinguished Chair in Pharmacology; Raymond and Ellen Willie Distinguished Chair in Molecular Neuropharmacology in Honor of Harold B. Crasilneck, Ph.D. School Medical School Department Pharmacology | Biochemistry Graduate Programs Cell and Molecular Biology Biography Dr. David J. Mangelsdorf received his BS in Biology and Chemistry from Northern Arizona University in Flagstaff (1981) and his PhD in Biochemistry from the University of Arizona in Tucson (1987). He did his postdoctoral studies at The Salk Institute for Biological Studies. Since 1993 he has been at UT Southwestern, where he currently is Professor and Chair of the Department of Pharmacology, and an Investigator of the Howard Hughes Medical Institute. He holds the Raymond and Ellen Willie Distinguished Chair in Molecular Neuropharmacology, in Honor of Harold B. Crasilneck, PhD and the Alfred G. Gilman Distinguished Chair in Pharmacology, and he is a member of the National Academy of Sciences. Dr. Mangelsdorf runs a joint laboratory with Dr. Steven Kliewer, and together their research team is focused on nuclear receptor regulation of metabolism. Their early work identifying the ligands and physiologic functions of a number of orphan nuclear receptors led them to discover two new signaling pathways mediated by the endocrine factors FGF19 and FGF21, which govern nutrient metabolism during feeding and fasting. Together, this work has uncovered potential therapeutic targets for diseases such as cholestasis, type 2 diabetes, and obesity. The Mangelsdorf/Kliewer lab also discovered the existence of a nuclear receptor pathway in parasitic nematodes, and has shown that pharmacophores that target this pathway may represent a new class of anthelmintic agents. Education Undergraduate Northern Arizona University , Aquatic Biology Graduate School University of Arizona (1987) Research Interest Nuclear receptors in physiology and disease Nutrient metabolsim and regulation of energy expenditure Roles of FGF19 and FGF21 in metabolism and behavior Targeting nuclear receptors in parasites Publications Featured Publications Characterization of the endogenous DAF-12 ligand and its use as an anthelmintic agent in Strongyloides stercoralis. Wang Z, Cheong MC, Tsien J, Deng H, Qin T, Stoltzfus JD, Jaleta TG, Li X, Lok JB, Kliewer SA, Mangelsdorf DJ, Elife 2021 12 10 Pancreatitis is an FGF21-deficient state that is corrected by replacement therapy. Hernandez G, Luo T, Javed TA, Wen L, Kalwat MA, Vale K, Ammouri F, Husain SZ, Kliewer SA, Mangelsdorf DJ, Sci Transl Med 2020 Jan 12 525 The Hormone FGF21 Stimulates Water Drinking in Response to Ketogenic Diet and Alcohol. Song P, Zechner C, Hernandez G, Cánovas J, Xie Y, Sondhi V, Wagner M, Stadlbauer V, Horvath A, Leber B, Hu MC, Moe OW, Mangelsdorf DJ, Kliewer SA Cell Metab. 2018 Apr FGF21 Is an Exocrine Pancreas Secretagogue. Coate KC, Hernandez G, Thorne CA, Sun S, Le TD, Vale K, Kliewer SA, Mangelsdorf DJ Cell Metab. 2016 Dec FGF21 Regulates Sweet and Alcohol Preference. Talukdar S, Owen BM, Song P, Hernandez G, Zhang Y, Zhou Y, Scott WT, Paratala B, Turner T, Smith A, Bernardo B, Müller CP, Tang H, Mangelsdorf DJ, Goodwin B, Kliewer SA Cell Metab. 2015 Dec The Nuclear Receptor DAF-12 Regulates Nutrient Metabolism and Reproductive Growth in Nematodes. Wang Z, Stoltzfus J, You YJ, Ranjit N, Tang H, Xie Y, Lok JB, Mangelsdorf DJ, Kliewer SA PLoS Genet. 2015 Mar 11 3 e1005027 Tissue-specific actions of the metabolic hormones FGF15/19 and FGF21. Owen BM, Mangelsdorf DJ, Kliewer SA Trends Endocrinol. Metab. 2015 Jan 26 1 22-29 Nuclear Receptors, RXR, and the Big Bang. Evans RM, Mangelsdorf DJ Cell 2014 Mar 157 1 255-266 FGF21 regulates metabolism and circadian behavior by acting on the nervous system. Bookout AL, de Groot MH, Owen BM, Lee S, Gautron L, Lawrence HL, Ding X, Elmquist JK, Takahashi JS, Mangelsdorf DJ, Kliewer SA Nat. Med. 2013 Aug FGF21 contributes to neuroendocrine control of female reproduction. Owen BM, Bookout AL, Ding X, Lin VY, Atkin SD, Gautron L, Kliewer SA, Mangelsdorf DJ Nat. Med. 2013 Aug Results 1-10 of 220 1 2 3 4 5 Next Last Honors & Awards Honorary Doctor of Humane Letters, Northern Arizona University (2016) The Rolf Luft AwardKarolinska Institutet, for outstanding contributions in endocrinology and diabetes research. (2012) Docteur Honoris Causa, Universite Blaise Pascal (2008) National Academy of Sciences (2008) Edith and Peter O’Donnell Award in MedicineThe Academy of Medicine, Engineering and Science of Texas (2007) Transatlantic MedalThe European Society of Endocrinology (2006) Gerald D. Aurbach AwardThe Endocrine Society (2004) Heinrich Wieland PrizeBoehringer Ingelheim (2003) Adolf Windaus PrizeWork in the field of bile acid research (2000) John J. Abel Award in PharmacologyAmerican Society for Pharmacology and Experimental Therapeutics (1997) Professional Associations/Affiliations American Association for Cancer Research American Society for Pharmacology and Experimental Therapeutics National Academy of Sciences (2008) The Academy of Medicine, Engineering and Science of Texas (2008) The Endocrine Society