David J. Mangelsdorf

The University of Texas Southwestern Medical Center


Election Year: 2008
Primary Section: 42, Medical Physiology and Metabolism
Membership Type: Member

Research Interests

My research interest is in the mechanism of action of nuclear receptors, a family of ligand-dependent transcription factors. I have characterized the ligands and physiologic functions for a number of these receptors including LXRs, which bind oxysterols; FXR, which binds bile acids; and PPARs, which bind fatty acids. Recently, our lab discovered two new hormones, FGF15 and FGF21, that are down-stream targets of FXR and PPARalpha, respectively. Our study of these two nuclear receptor/FGF endocrine pathways has led to an understanding of how the body regulates nutrient metabolism during feeding and fasting. A second area of research in our laboratory has resulted in the identification of the hormonal ligands for the C. elegans nuclear receptor, DAF-12. This receptor governs the commitment of nematode worms to enter one of two developmental states: a long-lived, developmentally arrested state called dauer diapause, or, a progressive developmental state that results in maturation to reproductive adults. The discovery of DAF-12 ligands has broad implications for how nutrient availability can affect longevity and reproduction. Because of their involvement in a number of diseases such as atherosclerosis, diabetes, obesity, and even parasitic infections, we are exploring the potential of these nuclear receptors as future therapeutic targets.

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