Postdoctoral positions available to study the mechanisms of action and regulation of a newly discovered transcription factor, termed “carbohydrate response element binding protein, ChREBP”. ChREBP is one of two essential transcription factors in liver responsible for lipogenesis, ChREBP increases the transcription of all lipogenic enzyme genes in response to high carbohydrate diets. Our goal is to understand how excess glucose, independently of insulin, activates lipogenic enzyme gene transcription. We have developed ChREBP-knockout mice and genetic crosses with ob/ob mice. Generation of additional “double knockout” mice with deficiencies in ChREBP and other genes involved in the regulation of carbohydrate and fat metabolism are planned. Ongoing investigations are using physiological, biochemical and molecular biology techniques to characterize the altered phenotypes of the genetically modified mice. Our future research focuses on roles of ChREBP in appetite control in hypothalamus. We are seeking candidates with biochemical, molecular biology, or obesity/diabetes interest and backgrounds that have earned a Ph.D. or MD degree in one of these areas.
(Selected references):
(1) Yamashita, H.,Takenoshita, M., Sakurai, M., Bruick, R.K., Henzel, W.J., Shillinglaw, W., Arnot, D., and Uyeda, K.,(2001) A Glucose-Responsive Transcription Factor that regulates Carbohydrate Metabolism in the Liver. Proc. Natl. Acad. Sci. 98, 9116-9121.
(2) Kawaguchi, T., Takenoshita, M., Kabashima, T., and Uyeda, K. (2001) Glucose and cAMP Regulate L-type Pyruvate Kinase Gene by Phosphorylation/Dephosphorylation of the Carbohydrate Response Element Binding Protein. Proc. Natl. Acad. Sci. 98, 13710 − 13715.
(3) Kawaguchi, T., Osatomi, K, Yamashita, H., Kabashima, T., and Uyeda, K. (2002) Mechanism of Fatty Acids “Sparing Effect” on Glucose-induced Transcription: Regulation of Carbohydrate Response Element Binding Protein by AMP-Activated Protein Kinase. J. Biol. Chem. 277, 3829-3835.
(4) Kabashima, T., Kawaguchi, T., and Uyeda, K. (2003) Xylulose-5-phosaphate Activated Protein Phosphatase is Mechanism of Hepatic Glucose-induced Lipogenesis. Proc. Natl. Acad. Sci. USA 100, 5107-5112.
(5) Jin, E. S., Uyeda, K., Kawaguchi, T., Burgess, S., Malloy, C. R., and Sherry, A. D. (2003) Increased hepatic fructose 2,6-bisphosphate after an oral glucose load does not affect gluconeogenesis. J. Biol. Chem. 278, 28427-28433.
(6) Iizuka, K., Bruick, R.K., Liang, G., Horton, J.D., and Uyeda, K. (2004) Deficiency of carbohydrate response element binding protein (ChREBP) reduces lipogenesis as well as glycolysis. Proc. Natl. Acad. Sci. USA 101, 7281-7286.
(7) Ishii, S.,Iizuka, K., Miller, B.C., Uyeda, K.(2004) Carbohydrate response element binding protein directly promotes lipogenic gene transcription PNAS 101, 15597-15602.
(8)Uyeda K, Repa JJ.Carbohydrate response element binding protein, ChREBP, a transcription factor coupling hepatic glucose utilization and lipid synthesis.
Cell Metab. 2006 Aug;4(2):107-10. Review.
(9)Burgess SC, Iizuka K, Jeoung NH, Harris RA, Kashiwaya Y, Veech RL, Kitazume T, Uyeda K. Carbohydrate-response element-binding protein deletion alters substrate utilization producing an energy-deficient liver.J Biol Chem. 2008 Jan 18;283(3):1670-8. Epub 2007 Nov 27
If you are interested, please send your curriculum vitae and names of references to:

Kosaku Uyeda, Ph.D.. Biochemistry Dept. University of Texas Southwestern Medical Center and VA. 4500 S Lancaster Rd. Dallas, TX 75216. Tel 214-857-0318, E mail:kosaku.uyeda@utsouthwestern.edu. FAX 214-857-0340.