Proceedings of the National Academy of Sciences of the United States of America

About the PNAS Member Editor
Name Mangelsdorf, David J.
Location The University of Texas Southwestern Medical Center
Primary Field Medical Physiology and Metabolism
 Election Citation
Mangelsdorf's work on nuclear receptors led to landmark discoveries of how regulatory pathways govern cholesterol and bile acid homeostasis. He defined crucial signal-transduction networks in their entirety by identifying the ligands, target genes, physiological functions, and molecular mechanisms for orphan nuclear receptors.
 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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