Steven A. Kliewer

The University of Texas Southwestern Medical Center


Primary Section: 42, Medical Physiology and Metabolism
Membership Type:
Member (elected 2015)

Biosketch

Steven Kliewer is a molecular biologist recognized for his work on nuclear hormone receptors and their roles in regulating metabolism. He earned his ScB in biochemistry from Brown University and his PhD in molecular biology from UCLA, followed by postdoctoral training as a Jane Coffin-Childs fellow at the Salk Institute for Biological Studies. From 1993-2002, he led a group pursuing nuclear receptors as drug targets at GlaxoSmithKline in Research Triangle Park, North Carolina. In 2002, he joined the University of Texas Southwestern Medical Center, where he is professor of Molecular Biology and Pharmacology and holds the Nancy B. and Jake L. Hamon Distinguished Chair in Basic Cancer Research. His research accomplishments include the discovery that the thiazolidinedione diabetes drugs act through the nuclear fatty acid receptor, PPAR-gamma; and the discovery of the xenobiotic receptor, PXR, and its essential role in a common class of drug-drug interactions. His awards include the Adolf Windaus Prize for Bile Acid Research, the Endocrine Society Ernst Oppenheimer Award, and the ASPET John J. Abel Award in Pharmacology.

Research Interests

Steven Kliewer’s laboratory, which he runs jointly with David Mangelsdorf, has a longstanding interest in nuclear receptors and hormone action, especially as they relate to metabolism. Their ongoing research revolves around two broad projects. First, they study the physiology and pharmacology of two atypical fibroblast growth factors, FGF15/19 and FGF21, which act as hormones. They have shown that FGF15/19 and FGF21 regulate metabolism and related processes in response to feeding and fasting, respectively. They have further shown that pharmacologically, FGF15/19 and FGF21 cause weight loss and improve insulin action in obese animals by acting on the brain. They are currently elucidating the molecular pathways through which FGF15/19 and FGF21 exert their physiologic and pharmacologic effects. In a second project, they are studying the nuclear hormone receptor DAF12, which is present in roundworms and parasitic nematodes, where it regulates metabolism and the reproductive cycle. The laboratory is investigating whether drugs that target DAF12 can be used as vermicides against parasites that infect humans, livestock and plants.

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