X. Charlie Dong, Ph.D.
Department of Biochemistry and Molecular Biology
Indiana University School of Medicine
John D. Van Nuys Medical Science Building
635 Barnhill Drive, Room 1021D
Indianapolis, Indiana 46202-5126
Phone: (317) 278-1097
Facsimile: (317) 274-4686
B.S. in Biology, 1991, Shandong Normal University, Jinan, China
M.S. in Genetics, 1994, Institute of Genetics, Chinese Academy of Sciences, Beijing, China
Ph.D. in Molecular, Cellular, and Developmental Biology, 2002, Ohio State University, Columbus, OH
Postdoctoral fellow, 2003-2008, Harvard Medical School, Children's Hospital Boston, Joslin Diabetes Center, Boston, MA
Area of Study
Gene regulation by hormones and nutrients in metabolic and energy homeostasis; transcriptomic and proteomic dissection of metabolic syndrome including diabetes and obesity. More details...
Selected Recent Publications
Sadagurski M*, Dong XC*, Myers MG, White MF. Irs2 and Irs4 synergize in non-LepRb neurons to control energy balance and glucose homeostasis. Mol Metab. 2013 Oct. 25. [Epub ahead of print], * Co-first authors.
He G, Zhang YW, Lee JH, Zeng SX, Wang YV, Luo Z, Dong XC, Viollet B, Wahl GG, Lu H. AMP-Activated Protein Kinase Induces p53 by Phosphorylating MDMX and Inhibiting Its Activity. Mol Cell Biol. 2014 Jan;34(2):148-57.
Riehle C, Wende AR, Sena S, Pires KM, Pereira RO, Zhu Y, Bugger H, Frank D, Bevins J, Chen D, Perry CN, Dong XC, Valdez S, Rech M, Sheng X, Weimer BC, Gottlieb RA, White MF, Abel ED. Insulin receptor substrate signaling suppresses neonatal autophagy in the heart. J Clin Invest. 2013 Dec 2;123(12):5319-33.
Tao R, Xiong X, Depinho RA, Deng CX, Dong XC. FoxO3 transcription factor and Sirt6 deacetylase regulate LDL-cholesterol homeostasis via control of the proprotein convertase subtilisin/kexin type 9 (Pcsk9) gene expression. J Biol Chem. 2013 Aug 23. [Epub ahead of print]
Xiong X, Tao R, Depinho RA, Dong XC. Deletion of Hepatic FoxO1/3/4 Genes in Mice Significantly Impacts on Glucose Metabolism through Downregulation of Gluconeogenesis and Upregulation of Glycolysis. PLoS One. 2013 Aug 28;8(8):e74340.
Tao R, Xiong X, Harris RA, White MF, Dong XC. Genetic inactivation of pyruvate dehydrogenase kinases improves hepatic insulin resistance induced diabetes. PLoS One. 2013 Aug 5;8(8):e71997.
Tao R, Xiong X, Depinho RA, Deng CX, Dong XC. Hepatic SREBP-2 and cholesterol biosynthesis are regulated by FoxO3 and Sirt6. J Lipid Res. 2013 Jul 23. [Epub ahead of print]
Lin CW, Zhang H, Li M, Xiong X, Chen X, Chen X, Dong XC, Yin XM. Pharmacological promotion of autophagy alleviates steatosis and injury in alcoholic and non-alcoholic fatty liver conditions in mice. J Hepatol. 2013; 58(5):993-9. PMCID: PMC3634371
Dhurandhar EJ, Krishnapuram R, Hegde V, Dubuisson O, Tao R, Dong XC, Ye J, Dhurandhar NV. E4orf1 improves lipid and glucose metabolism in hepatocytes: a template to improve steatosis & hyperglycemia. PLoS One 2012; 7(10):e47813. PMCID: PMC3479113
Zhang S, Liu S, Tao R, Wei D, Chen L;, Shen W, Yu Z, Wang L, Dong XC, Zhang ZY. A highly selective and potent PTP-MEG2 inhibitor with therapeutic potential for type 2 diabetes. J Am Chem Soc. 2012; 134(43):18116-24. PMCID: PMC3505080
Xiong X, Tao R, DePinho RA, Dong XC. The autophagy-related gene 14 (Atg14) is regulated by forkhead box O transcription factors and circadian rhythms and plays a critical role in hepatic autophagy and lipid metabolism. J. Biol. Chem. 2012; 287(46):39107-14. PMCID: PMC3493951
Dong XC. Sirtuin biology and relevance to diabetes treatment. Diabetes Management 2012; 2(3):243-257. PMCID: PMC3458714
Sadagurski M, Cheng Z, Rozzo A, Palazzolo I, Kelley GR, Dong X, Krainc D, White MF. IRS2 increases mitochondrial dysfunction and oxidative stress in a mouse model of Huntington disease. J Clin Invest. 2011;121(10):4070-81. PMCID: PMC3195462
Tao R, Wei D, Gao H, Liu Y, DePinho RA, Dong XC. Hepatic FoxOs regulate lipid metabolism via modulation of expression of the nicotinamide phosphoribosyltransferase gene. J. Biol. Chem. 2011; 286(16):14681-90. PMCID: PMC3077665
Wei D, Tao R, Zhang Y, White MF, Dong XC. Feedback regulation of hepatic gluconeogenesis through modulation of SHP/Nr0b2 gene expression by Sirt1 and FoxO1. Am J Physiol Endocrinol Metab. 2011;300(2):E312-20. PMCID: PMC3043623
Cheng Z, Guo S, Copps K, Dong X, Kollipara R, Rodgers JT, Depinho RA, Puigserver P, White MF. Foxo1 integrates insulin signaling with mitochondrial function in the liver. Nat Med. 2009;15(11):1307-11
Guo S, Copps KD, Dong X, Park S, Cheng Z, Pocai A, Rossetti L, Sajan M, Farese RV, White MF. The Irs1 branch of the insulin signaling cascade plays a dominant role in hepatic nutrient homeostasis. Mol Cell Biol. 2009; 29(18):5070-83. PMCID: PMC2738277
Dong, XC, Copps KD, Guo S, Li Y, Kollipara R, DePinho RA, White MF. Inactivation of hepatic Foxo1 by insulin signaling is required for adaptive nutrient homeostasis and endocrine growth regulation. Cell Metab. 2008; 8(1): 65-76. PMCID: PMC2929667
Li D, Yin X, Zmuda EJ, Wolford CC, Dong X, White MF, Hai T. The repression of IRS2 gene by ATF3, a stress-inducible gene, contributes to pancreatic beta-cell apoptosis. Diabetes 2008; 57(3): 635-644.
Giraud J, Haas M, Feener EP, Copps KD, Dong X, Dunn SL, White MF. Phosphorylation of Irs1 at SER-522 inhibits insulin signaling. Mol. Endocrinol. 2007; 21(9): 2294-2302.
Dong X, Park S, Lin X, Copps K, Yi X, and White MF. Irs1 and Irs2 signaling is essential for hepatic glucose homeostasis and systemic growth. J. Clin. Invest. 2006; 116(1): 101-114. PMCID: PMC1319221
Park S, Dong X, Fisher TL, Dunn S, Omer AK, Weir G, and White MF. Exendin-4 uses Irs2 signaling to mediate pancreatic beta cell growth and function. J. Biol. Chem. 2006; 281(2): 1159-1168
Diabetes and obesity have both reached epidemic proportions in the United States. It is becoming urgent to elucidate the pathological mechanisms of these health problems. Improper gene regulation by transcription factors and coregulators plays a crucial role in the pathogenesis of these metabolic diseases. This laboratory will focus on two key groups of factors that are emerging as critical regulators in nutrient and energy homeostasis. They are Forkhead box O transcription factors (Foxos) and NAD+-dependent deacetylase Sirtuin 1 (Sirt1). Foxos belong to a large family of transcription factors that share a conserved DNA-binding domain named "Forkhead box". Sirt1 is a mammalian homolog of yeast silent information regulator 2 (Sir2), a well-known longevity gene. The transcriptional activity of Foxos is regulated by both insulin-stimulated phosphorylation through Akt and by NAD+-mediated deacetylation through Sirt1. Foxos and Sirt1 have been critically implicated in the regulation of glucose and lipid homeostasis, however, the underlying molecular mechanisms are still poorly understood. Particularly, it is not yet clear why the same Sirt1-Foxo interaction induces one set of genes but suppresses another set in the same cells, and how these factors function differently in different tissues. In the next few years, we will address some of these important aspects of the problem by using both cell-based and whole-animal systems. As a gene target of Foxo1, pyruvate dehydrogenase kinase 4 (PDK4) has been suggested to play a critical role in glucose homeostasis through regulation of pyruvate dehydrogenase activity. Moreover, expression of PDK4 has also been shown to be elevated in muscle and liver of diabetic animal models, however, the regulatory mechanism is not clear. We will explore how hormonal and nutritional signals regulate the expression of PDK4 in both cell-based and whole-animal systems. Overall, our goal is to elucidate the molecular mechanisms that control nutrient and energy homeostasis and find desirable drug targets for therapeutic treatment of diabetes and obesity.