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David Mangelsdorf, PhD
Endowed Title: Distinguished Chair in Pharmacology
Raymond and Ellen Willie Distinguished Chair in Molecular Neuropharmacology, in Honor of Harold B. Crasilneck, Ph.D.
Integrative Biology
Contact Information
UT Southwestern Medical Center
5323 Harry Hines Boulevard
Dallas, Texas 75390
Office Phone: 214-645-5957
Office Fax: 214-645-5969
Biography
Dr. David J. Mangelsdorf was born in Davenport, Iowa in 1958. He received his BS (summa cum laude) 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 (1987-1993). Since 1993 he has been at UT Southwestern as Assistant Professor (1993-97), Associate Professor (1997-2000) and Professor (2000-present). In 2006, Dr. Mangelsdorf became Chair of the Department of Pharmacology. He also holds the Beatrice and Miguel Elias Distinguished Chair in Biomedical Science and has a secondary appointment in the Department of Biochemistry. Dr. Mangelsdorf has also been an Investigator of the Howard Hughes Medical Institute since coming to Dallas in 1993.
Dr. Mangelsdorf’s research program is focused on the mechanism of action of nuclear hormone receptors. These receptors orchestrate the body’s response to a myriad of crucial hormones, which include the steroid hormones, thyroid hormone, and vitamins D and A. His interest in this field began as a graduate student, where his research on vitamin D resulted in the cloning of the vitamin D receptor. As a postdoctoral fellow with Dr. Ronald Evans at The Salk Institute, he discovered several of the first orphan receptors, including the retinoid X receptor, RXR, and its ligand, 9-cis retinoic acid. This was the first ligand to be discovered for an orphan nuclear receptor and this finding ushered in the era of orphan receptor research. After moving to UT Southwestern, Dr. Mangelsdorf discovered that oxysterols are the endogenous ligands for the liver X receptors (LXRs). This work revealed the long sought-after mechanism by which the body senses and disposes of excess cholesterol. Subsequent research from his laboratory has led to the identification of the endogenous ligands and physiologic functions for several other metabolically important receptors, including the bile acid receptor (FXR), the vitamin D receptor (VDR), and the xenobiotic receptor (PXR). An important contribution of his work has been the finding that these receptors represent a family of unique lipid-sensing proteins that govern lipid metabolism. These discoveries have led to the identification of several new drug targets and unexpected insights into human disease. More recently, his laboratory discovered ligands for the C. elegans nuclear receptor, DAF-12, which are the first hormonal ligands to be discovered for an invertebrate orphan receptor.
Education
| Graduate School | University of Arizona (1987) |
Research Interests
Publications
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
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
Repa, J.J., Turley, S.D., Lobaccaro, J.A., Medina, J., Li, L., Lustig, K., Shan , B., Heyman, R.A., Dietschy, J.M., and Mangelsdorf, D.J. , Science , 2000; (289):1524-1529
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
Janowski, B.A., Willy, P.J., Rama Devi, T., Falck, J.R., and Mangelsdorf, D.J. , Nature , 1996; (383):728-731
Inagaki, T., Lin, V.Y., Goetz, R., Mohammadi, Mangelsdorf, D.J., Kliewer, S.A. , Cell Metabolism , 2008; (8):77-83
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
Umetani, M., Domoto, H., Gormley, A., Yuhanna, I.S., Cummins, C.L., Javitt, N.B., Korach, K.S., Shaul, P.W., Mangelsdorf, D.J. , Nature Medicine , 2007; (13):1185-1192
Bookout, A.L., Jeong, Y., Downes, M., Yu, R.T., Evans, R.M., Mangelsdorf, D.M. , Cell , 2006; (126):789-799
Motola, D.L., Cummins, C.L., Rottiers, V., Sharma, K.K., Li, T., Li, Y., Suino-Powell, K., Xu, H.E., Auchus, R.J., Antebi, A., Mangelsdorf, D.J. , Cell , 2006; (124):1209-1223
Related Links
Honors/Awards
(2008)
The Academy of Medicine, Engineering and Science of Texas (2007)
The Endocrine Society (2004)
Work in the field of bile acid research (2000)
American Society for Pharmacology and Experimental Therapeutics (1997)