David Mangelsdorf, Ph.D.

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 Distinguished Chair in Pharmacology, and he is a member of the National Academy of Sciences.

Dr. Mangelsdorf’s research interests are focused on the mechanism of action of orphan nuclear receptors. Stemming from his early work with Ronald Evans at the Salk Institute and the discovery of RXR and its ligand (9-cis retinoic acid), his lab has since characterized ligands and physiologic functions for the LXRs, which bind oxysterols; FXR, which binds bile acids; and PPARs, which bind fatty acids. Together, these receptors govern nutrient metabolism during feeding and fasting, and they have become therapeutic targets for diseases such as atherosclerosis, cholestasis, and type 2 diabetes. Since 2003, Mangelsdorf has been working jointly with Dr. Steven Kliewer at UT Southwestern. The focus of their work has centered on two new nuclear receptor-initiated endocrine signaling pathways that govern feeding and fasting responses and are mediated by the fibroblast growth factors FGF19 and FGF21. Recently, their lab has also discovered the existence of an orthologous nuclear receptor pathway that is conserved in parasitic nematodes, and has shown that pharmacophores that target this pathway may represent a new class of vermicides.

 

Undergraduate	Northern Arizona University (), Aquatic Biology
Graduate School	University of Arizona (1987)

• Molecular Biology of Orphan Nuclear Receptors
• The Role of Nuclear Receptors in Lipid Metabolism
• Transcription Factors and Gene Expression

Featured Publications

FGF19 as a postprandial, insulin-independent activator of hepatic protein and glycogen synthesis.

Kir S, Beddow SA, Samuel VT, Miller P, Previs SF, Suino-Powell K, Xu HE, Shulman GI, Kliewer SA, Mangelsdorf DJ Science 2011 Mar 331 6024 1621-4

Endocrine Regulation of the Fasting Response by PPARalpha-mediated Induction of Fibroblast Growth Factor 21.

Inagaki, T., Dutchak, P., Zhao, G., Ding, X., Gautron, L., Parameswara, V., Li, Y., Goetz, R., Mohammadi, M., Esser, V., Elmquist, J.K., Gerard, R.D., Burgess, S.C., Hammer, R.E., Mangelsdorf, D.J., Kliewer, S.A. Cell Metabolism 2007 5 415-425

Identification of a nuclear receptor for bile acids.

Makishima, M., Okamoto, A.Y., Repa, J.J., Tu, H., Learned, R.M., Luk, A., Hull, M.V., Lustig, K.D., Mangelsdorf, D.J., and Shan, B. Science 1999 284 362-365

Cholesterol and bile acid metabolism are impaired in mice lacking the nuclear oxysterol receptor, LXRα.

Peet, D.J., Turley, S.D., Ma, W., Janowski, B.A., Lobaccaro, J.A., Hammer, R.E., and Mangelsdorf, D.J. Cell May 1998 93 693-704

Identification of an oxysterol signaling pathway mediated by the nuclear receptor, LXR-alpha

Janowski, B.A., Willy, P.J., Rama Devi, T., Falck, J.R., and Mangelsdorf, D.J. Nature 1996 383 728-731

Fibroblast growth factor 21 promotes bone loss by potentiating the effects of peroxisome proliferator-activated receptor ?

Wei W, Dutchak PA, Wang X, Ding X, Wang X, Bookout AL, Goetz R, Mohammadi M, Gerard RD, Dechow PC, Mangelsdorf DJ, Kliewer SA, Wan Y Proceedings of the National Academy of Sciences of the United States of America 2012 Feb

Fibroblast Growth Factor-21 Regulates PPAR? Activity and the Antidiabetic Actions of Thiazolidinediones.

Dutchak PA, Katafuchi T, Bookout AL, Choi JH, Yu RT, Mangelsdorf DJ, Kliewer SA Cell 2012 Feb 148 3 556-67

Inhibition of growth hormone signaling by the fasting-induced hormone FGF21.

Inagaki, T., Lin, V.Y., Goetz, R., Mohammadi, Mangelsdorf, D.J., Kliewer, S.A. Cell Metabolism 2008 8 77-83

Endocrine Regulation of the Fasting Response by PPARalpha-mediated Induction of Fibroblast Growth Factor 21.

Inagaki, T., Dutchak, P., Zhao, G., Ding, X., Gautron, L., Parameswara, V., Li, Y., Goetz, R., Mohammadi, M., Esser, V., Elmquist, J.K., Gerard, R.D., Burgess, S.C., Hammer, R.E., Mangelsdorf, D.J., Kliewer, S.A. Cell Metabolism 2007 5 415-425

Anatomical profiling of nuclear receptor expression reveals a hierarchical transcriptional network.

Bookout, A.L., Jeong, Y., Downes, M., Yu, R.T., Evans, R.M., Mangelsdorf, D.M. Cell 2006 126 789-799

• The Rolf Luft Award
  Karolinska Institutet, for outstanding contributions in endocrinology and diabetes research. (2012)
• National Academy of Sciences
  (2008)
• Edith and Peter O’Donnell Award in Medicine
  The Academy of Medicine, Engineering and Science of Texas (2007)
• Transatlantic Medal
  The European Society of Endocrinology (2006)
• Gerald D. Aurbach Award
  The Endocrine Society (2004)
• Heinrich Wieland Prize
  Boehringer Ingelheim (2003)
• Adolf Windaus Prize
  Work in the field of bile acid research (2000)
• John J. Abel Award in Pharmacology
  American Society for Pharmacology and Experimental Therapeutics (1997)

• The Academy of Medicine, Engineering and Science of Texas (2008)
• American Association for Cancer Research
• American Society for Pharmacology and Experimental Therapeutics
• National Academy of Sciences
• The Endocrine Society