A. Personal Statement

BIOGRAPHICAL SKETCH Provide the following information for the Senior/key personnel and other significant contributors. Follow this format for each person. DO NOT EXCEED FOUR PAGES.

NAME POSITION TITLE V. Guoxun Chen Associate Professor eRA COMMONS USER NAME (credential, e.g., agency login) GCHEN6 EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable.) DEGREE INSTITUTION AND LOCATION MM/YY FIELD OF STUDY (if applicable) Virology and Molecular Wuhan University, Wuhan, China BS 1982-1986 Biology Virology and Molecular Wuhan University, Wuhan, China MS 1986-1989 Biology University of Texas Southwestern Medical Center Biochemistry and PhD 1997-2001 at Dallas, Dallas, USA Molecular Biology University of Texas Southwestern Medical Center Postdoctoral Insulin action and lipid 2001-2006 at Dallas, Dallas, USA training metabolism

A. Personal Statement My long-term research goal is to understand the roles of vitamin A (VA) in energy metabolism and the development of metabolic diseases, such as obesity and diabetes. Our lab has shown that VA status affects the obesity development in Zucker fatty rats, and retinoids regulate the expression of hepatic genes involved in the control of the hepatic glucose and lipid homeostasis. In addition, we have also shown that the insulin- regulated expression of the genes involved in hepatic glucose and fatty acid metabolism are impaired in the primary hepatocytes isolated from Zucker fatty, but not lean, rats fed ad libitum. I was the PI of a proposal supported by American Heart Association National Program to investigate the mechanism by which retinoids synergized with insulin to induce the hepatic glucokinase gene expression. My future career plan is to continue my research program and try to understand the roles of VA in the regulation of hepatic glucose and lipid metabolism, and in the development of insulin resistance and type 2 diabetes. The PI of this proposal has begun to recruit and train both undergraduate and graduate students since he established his independent research lab in the Department of Nutrition at the University of Tennessee in 2006. Three PhD and one MS graduate students have graduated from his lab since 2013. All of them graduated with research papers as the first authors. Rui Li, the PhD student, was selected as one of the ten finalists for American Society for Nutrition’s Graduate Student Research Awards Competition, supported by the Nutritional Sciences Council, and had presented his work at American Society for Nutrition’s Scientific Sessions and Annual Meeting at Experimental Biology 2013. Yang Li, another PhD student, was identified as a future leader in Nutrigenomics by the Nebraska Gateway to Nutrigenomics Award Selection Committee at the University of Nebraska – Lincoln in May 2013. Since 2006, the PI has published 22 peer-reviewed papers. His graduate students are co-authors in 12 of them.

B. Positions and Honors

Positions and Employment 1986-1989: Graduate Assistant, Department of Virology and Molecular Biology, Wuhan University, China 1989-1995: Research Scientist, Institute of Virology, Hubei Academy of Medical Sciences, China 1995-2001: Graduate Assistant, Department of Biochemistry, Gifford Laboratories and Touchstone Center for Diabetes Research, UT Southwestern Medical Center. 2001-07/2006: Postdoctoral fellow, with Michael Brown and Joseph Goldstein, Department of Molecular Genetics, UT Southwestern Medical Center. 08/2006-07/2012: Assistant Professor, Department of Nutrition, the University of Tennessee at Knoxville 08/2012-present: Associate Professor, Department of Nutrition, the University of Tennessee at Knoxville

Other Experience and Professional Memberships 2006-present: Member, American Diabetes Association 2006-present: Member, American Society for Nutrition (Chair-elect, Vitamin and Mineral RIS, 2012) 2007-present: Member, American Heart Association

Honors 1987, 1988: Excellent Graduate Student of Wuhan University, Wuhan, China. 1998: Outstanding scientific poster, GSO poster session, UT Southwestern Medical Center, Dallas, USA. 1999: Sigma-Xi, UT Southwestern Medical Center, Dallas, USA 1999-2001:Trainee, NIH training grant award, UT Southwestern Medical Center, Dallas, USA. 2009: NPAM Young Investigator Award at American Heart Association’s Scientific Sessions 2009

C. Selected Peer-reviewed Publications (Selected from _38_ peer-reviewed publications; please note: * indicating the publications which the PI’s graduate students are co-authors, and ** indicating the publications that the PI’s graduates students are the first authors)

Most relevant to the current application 1. Chen, G., Koyama, K., Yuan, X., Lee, Y., Zhou, Y.-T., O’Doherty, R., Newgard, C.B., and Unger, R.H., (1996) Disappearance of Body Fat in Normal Rats Induced by Adenovirus-Mediated Leptin Gene Therapy. Proc. Natl. Acad. Sci. USA. 93:14795- 14799. 2. Chen, G., Hohmeier, H., Gasa, R., Tran, V., and Newgard, C.B. (2000) Selection of Insulinoma Cell Lines With Resistance to IL-1ß and IFN--Induced Cytotoxicity. Diabetes: 49:562-570. 3. Chen, G., Hohmeier, H., and Newgard, C.B. (2001) Expression of the Transcription Factor STAT-1 in Insulinoma Cells Protects Against Cytotoxic Effects of Multiple Cytokines. J. Biol. Chem. 276: 766-772. 4. Yoon, J.C., Puigserver, P., Chen, G., Donovan, J., Wu, Z., Rhee, J., Adelmant, G., Kahn, C.R., Granner, D.K., Newgard, C.B., and Spiegelman, B.M.. (2001) Control of Hepatic Gluconeogenesis Through the Transcriptional Coactivator PGC-1. Nature: 413:131-138. 5. Chen, G., Liang G., Ou J., Goldstein, J.L., and Brown, M.S. (2004) Central Role for Liver X Receptor in Insulin-Mediated Activation of Srebp-1c Transcription and Stimulation of Fatty Acid Synthesis in Liver. Proc. Natl. Acad. Sci. USA 101: 11245- 11250. 6. Chen, G. (2007) Liver Lipid Molecules Induce PEPCK-C Gene transcription and Attenuate Insulin Action. Biochemical and Biophysical Research Communications. 361(3):805-10. 7. Chen, G., Zhang, Y., Lu, D., Li, N., and Ross, A.C. (2009) Retinoids Synergize with Insulin to Induce Hepatic Gck Expression. Biochemical Journal. 419(3):645-54. 8. **Li, R., Chen, W., Li, Y., Zhang, Y., and Chen, G. (2011) Retinoids Synergized with Insulin to Induce Srebp-1c Expression and Activated Its Promoter via the Two Liver X Receptor Binding Sites That Mediate Insulin Action. Biochemical and Biophysical Research Communications. 406(2):268-72 9. *Zhang, Y., Li, R., Chen, W., Li, Y., and Chen, G. (2011) Retinoids Induced Pck1 Expression and Attenuated Insulin-mediated Suppression of Its Expression via Activation of Retinoic Acid Receptor in Primary Rat Hepatocytes. Molecular and Cellular Biochemistry. 355(1):1-8. 10. *Zhang, Y., Li, R., Chen, W., Li, Y., Ge, Y., and Chen, G. (2011) Insulin-Regulated Srebp-1c and Pck1 mRNA Expression in Primary Hepatocytes from Zucker Fatty but not Lean Rats is Affected by Feeding Conditions. PLoS One 6(6):e21342 11. *Zhang, Y., Li, R., Li, Y., Chen, W., Zhao, S., and Chen, G. (2012) The Effects of Vitamin A Status on Obesity Development and Hepatic mRNA Levels of Key Genes for Glucose and Fatty Acid Metabolism in Zucker Lean and Fatty Rats. Biochemistry and Cell Biology. 90(4):548-57 12. **Li, Y., Zhang, Y., Li, R., Chen, W., Howell, M., Zhang, R., and Chen, G. (2012) The hepatic Raldh1 expression is elevated in Zucker fatty rats and its over-expression introduced the retinal-induced Srebp-1c expression in INS-1 cells. PLoS One 7(9):e45210 13. **Howell, M., Li, R., Zhang, R., Li, Y., Chen, W., and Chen, G. (2014) The expression of Apoc3 mRNA is regulated by HNF4α and COUP-TFII, but not acute retinoid treatments, in primary rat hepatocytes and hepatoma cells. Molecular and Cellular Biochemistry. 387:241-250 14. **Chen, W., Howell, M., Li, Y., Li, R., and Chen, G. (2014) Vitamin A and feeding statuses modulate the insulin-regulated gene expression in primary rat hepatocytes. PLoS ONE (Accepted) 15. **Li, R., Zhang, R., Li, Y., Zhu B., Chen, W., Zhang, Y., and Chen, G. (2014) A retinoic acid responsive element in the hepatic Gck promoter interacts with RARα, HNF4α, COUP-TFII, which affect the retinoic acid- and insulin- mediated Gck expression. Journal of Nutritional Biochemistry (Accepted, DOI: 10.1016/j.jnutbio.2014.04.009)

Additional recent publications of importance to the field (in chronological order)

D. Research Support

Ongoing Research Support

Completed Research Support Allen Foundation Inc Chen (PI) 07/01/2008- 06/30/2009 The Role of Vitamin A Metabolism on the Development of Obesity

Start-up fund (the University of Tennessee) Chen (PI) 08/01/2006- 07/30/2009 The hepatic lipid effects on the expression of genes in hepatocytes.

American Heart Association, Scientist Development Grant Chen (PI) 07/01/2009- 06/30/2013 The mechanism by which retinoids synergize with insulin to induce glucokinase gene expression