Dr. David J. Mangelsdorf was born in Davenport, Iowa in 1958. He received his B.S. (summa cum laude) in Biology and Chemistry from Northern Arizona University in Flagstaff (1981) and his Ph.D. 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 the University of Texas Southwestern Medical Center at Dallas as Assistant Professor (1993-97), Associate Professor (1997-2000) and Professor (2000-present). In 2006, Dr. Mangelsdorf became Chairman of the Department of Pharmacology. He also holds the Doris and Bryan Wildenthal Distinguished Chair in Medical Science and has an adjunct 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 for an invertebrate orphan receptor to be discovered.
