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Xiao Jian Sun, PhD

Academic Title:

Assistant Professor

Primary Appointment:

Medicine

Additional Title:

Assistant Professor

Location:

670 West Baltimore Street

Phone (Primary):

(410) 706-5865

Fax:

(410) 706-1622

Education and Training

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

 

 

 

Biosketch

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-        Assistant Professor in Division of Endocrinology, Diabetes and Nutrition, the Department of Medicine at University of Maryland School of Medicine

Research/Clinical Keywords

Insulin signaling, insulin resistance, obesity and diabetes

Highlighted Publications

 

Selected from over 60 peer review publications

 

1.    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

2.  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

3.  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

4.  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

5.  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

6.  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

7.  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

8.  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

9. 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

 

10. 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.

 

11. 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

 

12. Lehmann, R., Beck, A., Möschel, K., Schmidt, E.K., Deeg, M., Rapp, E., Sun, X.J., Kellerer, M., Voelter, W., Schleicher, E.D. , and Häring, H.U. (2002) Protein kinase C-z 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.

 

13. 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

 

14. 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.

 

15. 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 CqInhibits Insulin Signaling by Phosphrylating IRS1 at Ser1101. .  J. Biol. Chem.  279(44):45304-45307.

 

16. 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.

 

17. 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

 

18. 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.

 

19. 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. 296(4):E820-8.

 

20. Leng, S., Zhang, W., Zheng, Y.,  Liberman, Z., Li, Y., Rhodes, C. J., Polakiewicz, R. D. , Eldar-Finkelman, H.,and Sun, X.J., (2010). GSK3b mediates high glucose-induced ubiquitination and proteasome degradation of insulin receptor substrate-1. J. Endocrinol. 206, 171-181.

 

21. 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.

 

22. Xiaoquan Rao, Jeffrey A. Deiuliis,Georgeta Mihai, Juliet Varghese, Chang Xia, Matthew B. Frieman, Carole Sztalryd, Xiao Jian Sun, Michael J. Quon, Simeon I. Taylor, Sanjay Rajagopalan,  and Jixin Zhong (2017). Monocyte DPP4 Expression in Human Atherosclerosis Is Associated With Obesity and Dyslipidemia. Diabetes Care, in press.

 

23. Xiao J. Sun, Soohyun P. Kim, Dongming Zhang, Helen Sun, Qi Chao, Xin Lu, Zhekang Ying, Liwu Li, Robert R. Henry, Theodore P. Ciaraldi, Simeon I. Taylor, and Michael J. Quon, (2017).  Deletion of interleukin 1 receptor associated kinase 1 (IRAK-1) improves glucose tolerance primarily by increasing insulin sensitivity in skeletal muscle.  J. Biol. Chem. 292(29):12339-12350.

 

 

 

 

Additional Publication Citations

Book Chapter and Review

  1. Myers, M.G. Jr., Sun, X.J., and White, M.F. (1994). The IRS-1 signaling system. TIBS, 19(7), 289-293

  2. 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

Research Interests

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.

 

Dr. Sun’s recent research is involved in the investigation of molecular mechanism of insulin resistance in rodent models including mouse and rat. He has established mouse metabolic phenotyping techniques in the University of Maryland including IPGTT, ITT and hyperinsulinemic/euglycemic clamp. These techniques allow his group to investigate the molecular mechanism of insulin resistance in more physiologically relevant models and to engage in preclinical studies for potential drugs.

 

Grants and Contracts

Research Support

ADA Basic Science Award 1-14-BS-198                   Sun, Xiao Jian (PI)                                                             1/1/2014 – 12/31/2017

Repurposing the anti-Alzheimer drug donepezil, for treatment of metabolic and cardiovascular pathophysiology in metabolic syndrome

We hypothesize that donepezil increases peripheral concentrations of ACh to oppose ED leading to simultaneously improvement of metabolic and cardiovascular phenotypes in metabolic syndrome. Our Specific Aims are to evaluate 12 week oral donepezil therapy (vs. placebo) to improve metabolic and cardiovascular phenotypes of SHR rats, a rodent model for human metabolic syndrome with obesity, hypertension, fasting hyperinsulinemia, and IR. SHR and

littermate WKY control rats will undergo IPGTT, ITT, glucose clamp with tracer-labeled glucose, and measurement of blood pressure and circulating biomarkers for metabolic, pro-inflammatory, and endothelial dysfunction.

Role: PI

Completed Research Support

R29 AI41426-01                                                                                                                                                                Sun, Xiao Jian (PI)                                7/1/1996 – 8/31/2002

NIH

4PS Mediated Signaling Pathway in IL-4 System

This project focuses on the function of 4PS in IL-4 signal using 4PS transfected 32D cells. The molecular interaction between 4PS and IL-4 receptors will be investigated. Potential tyrosine kinase phosphorylation of 4PS in response to IL-4 will be identified and purified; potential 4PS regulated transcription factors will be identified and purified. The signal that links IL-4 receptors to the activation of gene transcription will be explored.  

 

R01 DK62336-02                                                                                                                                               Sun, Xiao Jian (PI)                             7/1/2004 – 6/30/2008

NIH

Mechanism of Insulin-induced Ubiquitination of IRS-1

This project investigates molecular mechanism of the ubiquitin-proteasome degradation of IRS-1. Specific ubiquitin enzymes and regulatory components in the proteasome required for insulin-induced IRS-1 degradation will be identified. Upstream signals that link to the ubiquitin-proteasome degradation of IRS-1 will be investigated in detail. 

Role: PI

 

ADA research grant                                                 Sun, Xiao Jian (PI)      7/1/2002 – 6/30/2005

ADA                                                                      

The Role of p52-IRS-1S789 Kinase in Insulin Resistance

This project investigates the serine/threonine phosphorylation of IRS-1 as one the molecular mechanisms of insulin resistance. It focuses on a p52-IRS-1S789 kinase which was identified in the lab to be the serine kinase associated with insulin resistance in rodents. p52-IRS-1S789 kinase will purified and cloned, and its role in insulin resistance will be investigated.

Role: PI

 

R56  DK081513-01A1                                                                                                Sun, Xiao Jian (PI)                             7/1/2009 – 6/30/2010

NIH

The role of serine phosphorylation of IRS-2 by ERK, mTOR and p70S6K in insulin resistance

This project investigates the serine phosphorylation of IRS-2 being the mechanism of hepatic insulin resistance. It focuses on the phosphorylation of IRS-2 mediated by ERK, mTOR and p70S6K.

Role:  PI

In the News

News in University of Maryland School of Medicine on September 12, 2017. "University of Maryaland School of Medicine Researches identify critical molecular link between inflammation and diabetes".

Community Service

Out reach program for High School Students who are interested in scientific research.

Professional Activity

2011-           :    Editorial board member of AJP-Endocrinology and Metabolism.

2016 – 2018:    Member of Research Grant Review Committee (RGRC), the scientific peer review panel for the Association’s Core Research Program.

Links of Interest