Steven Kliewer, Ph.D.

Steven Kliewer earned his BS in biochemistry from Brown University in 1985 and his PhD in molecular biology from the University of California, Los Angeles in 1990. From 1990-1993, he was a postdoctoral fellow in the laboratory of Dr. Ronald Evans at the Salk Institute for Biological Studies in La Jolla, CA, 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, thyroid hormone, retinoic acid, and peroxisome proliferator-activated receptors.

In 1993, he joined Glaxo, Inc. in Research Triangle Park, NC, where he 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 glitazone class of drugs, which ultimately led to the clinical development compound farglitazar. 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 Hamon Distinguished Chair in Basic Cancer Research. His research is focused on nuclear receptors and their roles in xenobiotic and lipid metabolism.

 

Undergraduate	Brown University (1985)
Graduate School	University of California-los Angeles (1990)

• Characterization of nuclear receptor signaling pathways
• Roles of nuclear receptors in liver and intestine
• Transcription factors and gene expression

Featured Publications

Orphan nuclear receptors: shifting endocrinology into reverse.

Kliewer, S.A., Lehmann, J.M., and Willson, T.M. Science 1999 284 757-760

An orphan nuclear receptor activated by pregnanes defines a novel steroid signaling pathway.

Kliewer, S.A., Moore, J.T., Wade, L., Staudinger, J.L., Watson, M.A., Jones, S.A., McKee, D.D., Oliver, B.B., Willson, T.M., Zetterstrom, R.H., Perlmann, T., and Lehmann, J.M. Cell 1998 92 73-82

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

A prostaglandin J2 metabolite binds peroxisome proliferator-activated receptor gamma and promotes adipocyte differentiation.

Kliewer, S.A., Lenhard, J.M., Willson, T.M., Patel, I., Morris, D.C., and Lehmann, J.M. Cell 1995 83 813-819

Retinoid X receptor interacts with nuclear receptors in retinoic acid, thyroid hormone, and vitamin D3 signalling.

Kliewer, S.A., Umesono, K., Mangelsdorf, D.J., and Evans, R.M. Nature 1992 355 446-449

Tissue-specific expression of beta KLOTHO and fibroblast growth factor receptor isoforms determines metabolic activity of FGF19 and FGF21

Kurosu H, Choi M, Ogawa Y, Dickson AS, Goetz R, Eliseenkova AV, Mohammadi M, Rosenblatt KP, Kliewer SA, Kuro-o M J. Biol. Chem. July 2007 [epub ahead of print]

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

Identification of a hormonal basis for gallbladder filling

Choi M, Moschetta A, Bookout AL, Peng L, Umetani M, Holmstrom SR, Suino-Powell K, Xu HE, Richardson JA, Gerard RD, Mangelsdorf DJ, Kliewer SA. Nat Med November 2006 12 1253-5

Regulation of antibacterial defense in small intestine by the nuclear bile acid receptor

Inagaki T., Moschetta A., Lee Y-K, Peng L., Zhao G., Downes M., Yu R.T., Shelton J.M., Richardson J.A., Repa J.J., Mangelsdorf D.J., Kliewer S.A. Proc Natl Acad USA March 2006 103 3920-5

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

• Endocrine Society Ernst Oppenheimer Award
  (2005)
• Aventis Innovative Investigator Award
  (2004)
• ISSX North American New Investigator Award
  (2003)
• ASPET John J. Abel Award in Pharmacology
  (2002)

• American Society for Pharmacology and Experimental Therapeutics
• The Endocrine Society