Xiao Jian Sun
1979: B.S. in Pharmacology at School of Pharmacology, Shanghai Medical University, Shanghai, China.
1982: M.S. in Biochemistry at School of Medicine, Shanghai Medical University, Shanghai, P.R. China
1986: Ph.D. in Biochemistry at Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China
1987-1989: Postdoctoral training at Dr. Jui-Yoa Chang's lab at Pharmaceutical Research Laboratories, Novartis, Basel, Switzerland (CIBA-GEIGY limited) on the mechanism of inhibitory effect of antithrombin III on thrombin.
1989-1994: Postdoctoral Fellow at Dr. Morris White's lab at Joslin Diabetes Center, Harvard Medical School, Boston on the mechanism of insulin action and signal transduction.
1986-1987: Lecturer in the Department of Biochemistry at Shanghai Medical University, Shanghai, P.R. China.
1989-1994: Research fellow in Joslin Diabetes Center, Harvard Medical School, Boston, MA.
1994-1995: Research Associate in Joslin Diabetes Center, Harvard Medical School, Boston, MA.
1994-1995: Instructor in Harvard Medical School, Boston, MA.
1995-1996: Senior research scientist, and GTST group leader in METABOLEX, Inc., Hayward, CA.
1996-2003: Assistant Professor in the Department of Medicine at the University of Vermont College of Medicine.
1997-2003: Faculty Member in the Cell and Molecular Biology Program, University of Vermont
1997-2003: Faculty member at the University of Vermont Graduate College.
2003-2010: Member of Committee on the Molecular Metabolism & Nutrition at The University of Chicago
2003-2010: Assistant Professor in the Department of Medicine at University of Chicago
2011-present: Assistant Professor in the Department of Medicine at University of Maryland School of Medicine
Dr. Xiao Jian Sun's research focuses on the molecular mechanism of insulin action and the molecular basis for insulin resistance. Insulin is a key hormone that regulates glucose and lipid metabolisms by well defined signaling pathway. In insulin sensitive cells, insulin signal pathway is continuously influenced by surrounding cellular signaling pathways (cross-talk) including nutrient, stress, growth factors and inflammation signaling pathways, resulting in dynamic alteration of insulin sensitivity, which is thought to contribute to the cause of insulin resistance. Insulin receptor substrate (IRS) -1 and -2 are key molecules in insulin signal pathway in insulin sensitive cells and tissues. Dr. Sun's researches have revealed two mechanisms that are involved in these signal cross-talks: serine phosphorylation of IRS-proteins and ubiquitin-proteasome degradation of IRS-proteins. It is supported by growing evidence that serine phosphorylation and degradation of IRS-proteins induced by nutrients, stress and inflammation attenuate cellular insulin action, resulting in insulin resistance. Dr. Sun has hypothesized that serine phosphorylation of IRS-proteins is the focal point of these cross-talks that alter insulin sensitivity. His lab is currently focused on the efforts to identify: 1) specific serine kinases downstream of these signaling pathways that can phosphorylate IRS-proteins; 2) ubiquitin enzymes and regulatory components that are required for the proteasome degradation of IRS-proteins. Results from these investigations should help to understand the molecular mechanism of insulin resistance and to provide an opportunity to identify new molecules involved in the regulation of insulin signaling and insulin resistance.
Selected Peer-Reviewed Publications
Sun, X.J., Rothenberg, P., Kahn, C.R., Backer, J.M., Araki, E., Wilden, P.A., Cahill, D.A., Goldstein, B.J. and White,M.F. (1991). Structure of the insulin receptor substrate IRS-1 defines a unique signal transduction protein. Nature,352, 73-77.
Sun, X.J., Miralpeix, M., Myers, M.G.Jr, Glasheen, E.M., Backer, J.M., Kahn, C.R. and White, M.F. (1992). The expression and function of IRS-1 in insulin signal transmission. J. Biol. Chem. 267 (31), 22662-22672.
Sun, X. J., Crimmins, D.L., Myers, M.G. Jr., Miralpeix, M. and F. White, M.F. (1993). Pleiotropic insulin signals are engaged by multisite phosphorylation of IRS-1. Mol. Cell. Biol. 13(12), 7418-7428
Sun, X.J., Wang, L-M., Zhang, Y., Yenush, L., Myers, Jr.,M.G., Glasheen, E., Lane, W., Pierce, J.H., and White, M.W., (1995). The role of IRS-2 in insulin and cytokine signaling. Nature, 377, 173-177.
Sun, X.J., Pons, S., Asano, T., Myers, Jr.,M.G., Glasheen, E., and White, M.W. (1996). The fyn tyrosine kinase bindsIRS-1 and forms a distinct signaling complex during insulin stimulation. J. Biol. Chem. 271, 10583-10587.
Sun, X.J., Wang, L-M., Zhang, Y., Pons, S., Yenush, L., Myers, Jr.,M.G., Glasheen, E., Lane, W., Jenkins, N., Pierce, J.H., and White, M.W. (1997). The IRS-2 gene on murine chromosome 8 encodes a unique signaling adapter for insulin and cytokine action. Mol. Endocrinol., 11, 251-262.
Sun, X.J., Goldberg, J.L., Qiao, L., and Mitchell, J.J. (1999). Insulin-induced IRS-1 degradation is mediated by the proteasome degradation pathway. Diabetes, 48, 1359-1364.
Qiao, L., Goldberg, J.L., Russell, J.C., and Sun, X.J. (1999). Identification of enhanced serine kinase activity in insulin resistance. J. Biol. Chem., 274(15), 10625-10632
Qiao, L., Zhande, R., Jetton, T.L., Zhou, G. and Sun, X.J. (2002). In vivo phosphorylation of IRS-1 at serine789 by a novel serine kinase in insulin resistant rodents. J. Biol. Chem. 277(29), 26530-26539
Jetton, T.L., Liu, Y.Q., Trotman, W.E., Nevin, P.W., Sun, X.J., Leahy, J.L. (2001) Enhanced insulin receptor substrate-2 expression in the regenerating pancreatic duct epithelium of 60% partial pancreatectomy rats. Diabetologia 44(11:2056-2065.
Zhande, R., Mitchell, J.J., Wu, J., and Sun, X.J. (2002) Molecular mechanism of insulin-induced degradation of IRS-1. Mol. Cell. Biol. 22(4), 1016-1026.
Lehmann, R., Beck, A., Maschel, K., Schmidt, E.K., Deeg, M., Rapp, E., Sun, X.J., Kellerer, M., Voelter, W., Schleicher, E.D. , and Harring, H.U. (2002) Protein kinase C-ς phosphorylates serine/threonine residues at the C-terminal binding motif of the tyrosine phosphatase SHP-2 of insulin receptor substrate 1. Signal Transduction. 1-2, 40-45.
Horike, N., Takemori, H., Katoh, Y., Doi, J., Min, L., Asano, T., Sun, X.J., Yamamoto, H., Kasayama, S., Muraoka, M., Nonaka, Y., Okamoto, M. (2003). Adipose-specific Expression, Phosphorylation of Ser794 in Insulin Receptor Substrate-1, and Activation in Diabetic Animals of Salt-inducible Kinase-2. J. Biol. Chem. 278(20):18440-18447
Li, Y., Eitan, S. Wu, J., Wu, J., Evans, C.J., Kieffer, B., Sun, X.J., and Polakiewicz, R.D. (2003) Morphine-induces desensitization of insulin receptor signaling. Molec. Cell Biol. 23(17), 6255-6266.
Li, Y., Eitan, Soos,T.J., Li, X., Wu, J., DeGennaro, M., Sun, X.J., Littman, D.R., Birnbaum, M.J., and Polakiewicz, R.D. (2004) Protein Kinase Cθ
Inhibits Insulin Signaling by Phosphrylating IRS1 at Ser1101. J. Biol. Chem. 279(44):45304-45307.
Zhande, R., Zhang, W., Zheng, Y., Pendleton, E., Li, Y., Polakiewicz, R., Sun, X.J., (2006) Dephosphorylation by default: A Potential mechanism for regulation of IRS-1, Akt and Erk1/2. J. Biol. Chem. 281(51):39071-39080.
Frédéric Tremblay, Sophie Brûlé, Sung Hee Um, Yu Li , Michael Krebs, Xiao Jian Sun, Michael Roden, Roberto D. Polakiewicz, George Thomas and André Marette, (2007) Identification of Ser1101 in IRS-1 as a target of S6K1 in nutrient and obesity-induced insulin resistance. Proc. Natl. Acad. Sci., USA, 104, 14056-14061
Ling He, Amin Sabet, Stephen Djedjos, Ryan Miller, Xiao Jian Sun, Mehboob A. Hussain, Sally Radovick and Fredric E. Wondisford. (2009) Metformin and Insulin Suppress Hepatic Gluconeogenesis by Inhibiting cAMP Signaling Through Phosphorylation of CREB Binding Protein (CBP). Cell 137, 635-646.
Kari E. Wong, Frances L. Szeto, Wenshuo Zhang, Honggang Ye, Juan Kong, Zhongyi Zhang, Xiao Jian Sun, Yan Chun Li, (2009) Involvement of the Vitamin D Receptor in Energy Metabolism: Regulation of Uncoupling Proteins. Am J. Physiol. Endocrinol. Metab. (in press)
Leng, S., Zhang, W., Zheng, Y., Liberman, Z., Li, Y., Rhodes, C. J., Polakiewicz, R. D. , Eldar-Finkelman, H., and Sun, X.J., (2010). GSK3ï¢ mediates high glucose-induced ubiquitination and proteasome degradation of insulin receptor substrate-1. J. Endocrinol. 206, 171-181.
Zheng, Y., Zhang, W., Pendleton, E., Leng, S., Wu, J., Chen, R., and Sun, X.J., (2010). Improved insulin sensitivity by caloric restriction is associated with reduction of ERK and p70S6K activities in the liver of obese Zucher rats. J. Endocrinol., 203, 337-347.
Book Chapters and Review
Myers, M.G. Jr., Sun, X.J., and White, M.F. (1994). The IRS-1 signaling system. TIBS, 19(7), 289-293
Sun, X.J. and Liu,F. (2009). Chapter 13: Phosphorylation of IRS-proteins Yin-Yang Regulation of Insulin Signaling. Vitamins and Hormones, Vol. 80:351-387 Academic Press/Elsevicer