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
E-mail: xcdong@iupui.edu
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, 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 Sep 19. [Epub ahead of print]
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 Apr 22;286(16):14681-90.
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 Feb;300(2):E312-20.
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 Nov;15(11):1307-11.
Guo S, Copps KD, Dong X, Park S, Cheng Z, Pocai A, Rossetti L, Sajan M, Farese RV, White MF. (2009) The Irs1 branch of the insulin signaling cascade plays a dominant role in hepatic nutrient homeostasis. Mol Cell Biol. 2009 Sep;29(18):5070-83.
Dong XC, Copps KD, Guo S, Li Y, Kollipara R, DePinho RA, and White MF. Inactivation of hepatic Foxo1 by insulin signaling is required for adaptive nutrient homeostasis and endocrine growth regulation. Cell Metab. 2008 Jul;8(1):65-76.
Li D, Yin X, Zmuda EJ, Wolford CC, Dong XC, White MF, and Hai T. The repression of IRS2 gene by ATF3, a stress-inducible gene, contributes to pancreatic beta-cell apoptosis. Diabetes. 2008 Mar;57(3):635-44.
Giraud J, Haas M, Feener EP, Copps KD, Dong XC, Dunn SL, White MF. Phosphorylation of Irs1 at SER-522 inhibits insulin signaling. Mol Endocrinol. 2007 Sep;21(9):2294-302.
Dong XC, 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 Jan;116(1):101-14.
Park S, Dong X, Fisher TL, Dunn S, Omer AK, Weir G, White MF. Exendin-4 uses Irs2 signaling to mediate pancreatic beta cell growth and function. J Biol Chem. 2006 Jan 13;281(2):1159-68.
Ghoshal K, Datta J, Majumder S, Bai S, Dong X, Parthun M, Jacob ST. Inhibitors of histone deacetylase and DNA methyltransferase synergistically activate the methylated metallothionein I promoter by activating the transcription factor MTF-1 and forming an open chromatin structure. Mol Cell Biol. 2002 Dec;22(23):8302-19.
Dong X, Ghoshal K, Majumder S, Yadav SP, Jacob ST. Mitochondrial transcription factor A and its downstream targets are up-regulated in a rat hepatoma. J Biol Chem. 2002 Nov 8;277(45):43309-18.
Majumder S, Ghoshal K, Datta J, Bai S, Dong X, Quan N, Plass C, Jacob ST. Role of de novo DNA methyltransferases and methyl CpG-binding proteins in gene silencing in a rat hepatoma. J Biol Chem. 2002 May 3;277(18):16048-58.
Ghoshal K, Majumder S, Li Z, Dong X, Jacob ST. Suppression of metallothionein gene expression in a rat hepatoma because of promoter-specific DNA methylation. J Biol Chem. 2000 Jan 7;275(1):539-47.
Research Interests
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.
