Steven Kliewer earned his BS in biochemistry from Brown University in 1985 and his PhD in molecular biology from UCLA in 1990. From 1990-1993, he was a postdoctoral fellow in the laboratory of Dr. Ronald Evans at the Salk Institute, where he began his studies on orphan nuclear receptors. During this period, he discovered the central role that the retinoid receptor RXR plays as an obligate heterodimer partner for the vitamin D receptor, thyroid hormone receptor, retinoic acid receptor, and PPARs.
In 1993, he joined Glaxo, Inc., where he co-founded a scientific group devoted to exploiting orphan nuclear receptors as drug discovery targets. Among his achievements at Glaxo was the discovery that the fatty acid receptor PPAR-gamma is the molecular target for the antidiabetic TZD class of drugs, including rosiglitazone and pioglitazone. He also discovered the xenobiotic receptor PXR and showed that it is responsible for an important class of drug-drug interactions. A practical consequence of this work is that new drugs can be screened efficiently for harmful interactions with other medications.
In 2002, he joined the faculty at UT Southwestern, where he is currently Professor of Molecular Biology and Pharmacology and holds the Nancy B. and Jake L. Hamon Distinguished Chair in Basic Cancer Research. He runs a joint laboratory with Dr. David Mangelsdorf that focuses on the roles of nuclear receptors and endocrine FGFs in regulating diverse aspects of physiology and pathophysiology, including metabolism and metabolic disease.
- Brown University (1985), Biochemistry
- Graduate School
- University of California UCLA (1990), Molecular Biology
- Endocrine FGFs
- Metabolism and metabolic disease
- Nuclear receptors
- Endocrine Regulation of the Fasting Response by PPARalpha-Mediated Induction of Fibroblast Growth Factor 21
- Inagaki T, Dutchak P, Zhao G, Ding X, Gautron L, Parameswara V, Li Y, Goetz R, Mohammadi M, Esser V, Elmquist JK, Gerard RD, Burgess SC, Hammer RE, Mangelsdorf DJ, Kliewer SA Cell Metab June 2007 5 415-25
- Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis
- Inagaki T., Choi M., Moschetta A., Peng L., Cummins C.L., McDonald J.G., Luo G., Jones S.A., Goodwin B., Richardson J.A., Gerard R.D., Repa J.J., Mangelsdorf D.J., Kliewer S.A. Cell Metab November 2005 2 217-225
- The human orphan nuclear receptor PXR is activated by compounds that regulate CYP3A4 gene expression and cause drug interactions.
- Lehmann JM, McKee DD, Watson MA, Willson TM, Moore JT, Kliewer SA J. Clin. Invest. 1998 Sep 102 5 1016-23
- An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor gamma (PPAR gamma).
- Lehmann, J.M., Moore, L.B., Smith-Oliver, T.A., Wilkison, W.O., Willson, T.M., and Kliewer, S.A. J. Biol. Chem 1995 270 12953-12956
- The Nuclear Receptor DAF-12 Regulates Nutrient Metabolism and Reproductive Growth in Nematodes.
- Wang Z, Stoltzfus J, You YJ, Ranjit N, Tang H, Xie Y, Lok JB, Mangelsdorf DJ, Kliewer SA PLoS Genet. 2015 Mar 11 3 e1005027
- FGF21 Acts Centrally to Induce Sympathetic Nerve Activity, Energy Expenditure, and Weight Loss.
- Owen BM, Ding X, Morgan DA, Coate KC, Bookout AL, Rahmouni K, Kliewer SA, Mangelsdorf DJ Cell Metab. 2014 Aug
- FGF21 regulates metabolism and circadian behavior by acting on the nervous system.
- Bookout AL, de Groot MH, Owen BM, Lee S, Gautron L, Lawrence HL, Ding X, Elmquist JK, Takahashi JS, Mangelsdorf DJ, Kliewer SA Nat. Med. 2013 Aug
- FGF19 as a postprandial, insulin-independent activator of hepatic protein and glycogen synthesis.
- Kir S, Beddow SA, Samuel VT, Miller P, Previs SF, Suino-Powell K, Xu HE, Shulman GI, Kliewer SA, Mangelsdorf DJ Science 2011 Mar 331 6024 1621-4
Honors & Awards
- National Academy of Sciences
- Falk Foundation Adolf Windaus Prize
- Endocrine Society Ernst Oppenheimer Award
- Aventis Innovative Investigator Award
- ISSX North American New Investigator Award
- ASPET John J. Abel Award in Pharmacology
- American Society for Pharmacology and Experimental Therapeutics
- The Endocrine Society