Skip to main content

Dong Lab

The research lab of Charlie Dong, PhD, is studying the mechanisms regulating nutrient homeostasis, energy expenditure, cell signaling, gene transcription, epigenetic control of chromatin remodeling in normal physiology, aging, cancer, diabetes, obesity, and alcoholic and non-alcoholic fatty liver diseases.

Active Research

The Dong Laboratory focuses on the pathogenesis of aging, cancer, diabetes, obesity, and fatty liver disease. Specifically, the laboratory team investigates the pathophysiological functions of forkhead box O transcription factors (Foxos) and NAD+-dependent deacetylases (Sirtuins) using cellular and animal model systems. This group is among the first to discover the link from the insulin signaling pathway to the NAD biogenesis and regulation. The Dong Lab also made significant contributions to the molecular mechanisms of triglyceride and cholesterol homeostasis, especially with regard to the role of Foxo3 and Sirt6 genes. Recently, this research team has demonstrated a novel role of Sesn3 in the regulation of mTOR signaling and insulin sensitivity. In addition, this lab has uncovered a novel function of Sirt6 in the regulation of glucose-stimulated insulin secretion from pancreatic beta cells.

Get Research Updates

To stay current on the medical research work at IU School of Medicine, follow the IU School of Medicine research blog, where investigators throughout the school’s academic departments statewide post updates about their work.

Blogs Hub

Aging

The Dong Lab is investigating the physiological and pathological aging processes at cell, organ and system levels. As Foxo transcription factors and Sirt6 are longevity-promoting factors, it is of importance to understand their biological functions. Both cell and animal models are used in this line of research.

Cancer

The Dong Lab is also actively investigating oncogenes and tumor suppressors and their role in the process of cell transformation and tumorigenesis. As the incidents of liver cancer is on the rise, the current focus of cancer research in the lab is to understand how the liver cancer is initiated in the first place.

Diabetes and Obesity

Owing to overnutrition and sedentary lifestyle in the current society, the prevalence of diabetes and obesity is steadily increasing. This laboratory is investigating molecular mechanisms that control the normal physiology and pathophysiology in diet-induced and genetic defect-induced diabetes and obesity. Both cell and animal models are used to illustrate the underlying mechanisms.

Alcoholic and Non-alcoholic Fatty Liver Diseases

Both ethanol consumption and overnutrition can cause excessive triglyceride accumulation in the liver, commonly called hepatic steatosis or fatty liver. The fatty liver disease can progress to more serious liver problems including hepatitis, fibrosis, cirrhosis, and even hepatocellular carcinoma. This laboratory is investigating the whole spectrum of the fatty liver disease and aiming to understand the mechanism of pathogenesis. Both in vitro and in vivo models will be used for the ongoing studies.

Current Research Funding

  • Regulation of hepatic lipid metabolism by a novel Foxo pathway
    NIH R01 DK091592 (PI), 3/1/12-2/28/18, 3.6 calendar

    Agency: NIH/NIDDK

    Goal: This project is to illustrate the molecular regulation of hepatic lipid metabolism

    Amount: $1,695,775

    Role: PI

  • Sestrin3 in the pathogenesis of alcoholic and non-alcoholic fatty liver disease
    NIH R01DK107682 (MPI/Liangpunsakul & Dong), 7/1/16 – 6/30/20, 2.4 calendar

    Agency: NIH/NIDDK

    Goal: To illustrate the molecular mechanisms underlying the Sestrin3 function in the development of fatty liver disease.

    Amount: $1,392,913

    Role: Co-PI

  • Role of sirtuin 6 in the protection of liver from the alcohol-induced liver injury
    NIH R21AA024550-01A1 (PI), 3/1/17 – 2/28/19, 2.4 calendar

    Agency: NIH/NIDDK

    Goal: To explore the hepatic protective function of sirtuin 6 against alcohol-induced tissue damage.

    Amount: $409,500

    Role: PI

  • Showalter Scholar
    Showalter Scholar Award (PI, 07/01/15 – 06/30/18,  .60 calendar

    Agency: IU School of Medicine and Showalter Trust Funds

    Goal: To enhance faculty research and career development.

    Amount: $75,000

    Role: PI

  • A precision therapeutic approach for nonalcoholic steatohepatitis NASH
    Indiana CTSI CTR, (MPI/Liu, Dong, Yeo), 07/01/16 – 6/30/18, .60 calendar

    Agency:  Indiana CTSI

    Goal:  To develop a collaborative team for the NASH translational research.

    Amount: $75,000

    Role: Co-PI

  • Epigenetic regulation of the pancreatic beta cell aging
    IUPUI RSFG-DONG (PI)   , 6/1/17-6/30/18, .60 calendar

    Agency: IUPUI

    Goal: This pilot grant aims to support the generation of additional preliminary data for an external grant application.

    Amount: $35,000

    Role: PI

  • Characterization of molecular signatures that distinguish excessive alcohol drinking from alcohol liver disease a pilot study
    Indiana CTSI CTR  (MPI/Liangpunsakul, Dong, Zhang C, and Zhang M), 10/1/17 – 9/30/19, .60 calendar

    Agency: Indiana CTSI

    Goal: This pilot study is to identify molecular profiles from alcohol heavy drinkers.

    Role: Co-PI

  • The role of Sestrin 3-regulated inflammatory pathways in post-traumatic epilepsy
    Indiana State Department of Health, Xu (PI), 7/1/17-6/30/19, .60 calendar

    Agency: Indiana State Department of Health

    Goal: This project is to illustrate the mechanism of Sestrin 3 in the protection against post-traumatic epilepsy.

    Amount: $160,000

    Role: Co-I

Recent Publications

A complete list of published work is available.

1. Dong XC. SCP4: A small nuclear phosphatase having a big effect on FoxOs in gluconeogenesis. Diabetes. 2018 Jan;67(1):23-25.  DOI: 10.2337/dbi17-0042

2. Tao R, Wang C, Stohr O, Qiu W, Hu Y, Miao J, Dong XC, Leng S, Stefater M, Stylopoulos N, Lin L, Copps KD, White MF. Inactivating hepatic follistatin alleviates hyperglycemia. Nat Med. 2018 Jul;24(7):1058-1069.  DOI: 10.1038/s41591-018-0048-0

3.  Kim HG, Huang M, Xin Y, Zhang Y, Zhang X, Wang G, Liu S, Wan J, Ahmadi AR, Sun Z, Liangpunsakul S, Xiong X, Dong XC. The epigenetic regulator SIRT6 protects the liver from alcohol-induced tissue injury by reducing oxidative stress in mice. J Hepatol. 2019 Nov;71(5):960-969.  DOI: 10.1016/j.jhep.2019.06.019

4. Liu Y, Kim HG, Dong E, Dong C, Huang M, Liu Y, Liangpunsakul S, Dong XC. Sesn3 deficiency promotes carcinogen-induced hepatocellular carcinoma via regulation of the hedgehog pathway. Biochim Biophys Acta Mol Basis Dis. 2019 Oct 1; 1865(10):2685-2693.  DOI: 10.1016/j.bbadis.2019.07.011

5.  Dong XC. PNPLA3-A potential therapeutic target for personalized treatment of chronic liver disease. Front. Med. 2019 Dec 17;6:304.  DOI: 10.3389/fmed.2019.00304

6.  Huang M, Kim HG, Zhong X, Dong C, Zhang B, Fang Z, Zhang Y, Lu X, Saxena R, Liu Y, Zhang C, Liangpunsakul S, Dong XC. Sesn3 protects against diet-induced nonalcoholic steatohepatitis in mice via suppression of the TGFb signal transduction. Hepatology. 2020 Jan;71(1):76-92.  DOI: 10.1002/hep.30820

7.  Vemuri S, Srivastava R, Mir Q, Hshemikhabir S, Dong XC, Janga SC. SliceIt: A genome-wide resource and visualization tool to design CRISPR/Cas9 screens for editing protein-RNA interaction sites in the human genome. Methods. 2020 Jun 1;178:104-113.  DOI: 10.1016/j.ymeth.2019.09.004

8.  Zhong X, Huang M, Kim HG, Zhang Y, Chowdhury K, Cai W, Saxena R, Schwabe RF, Liangpunsakul S, Dong XC. SIRT6 Protects Against Liver Fibrosis by Deacetylation and Suppression of SMAD3 in Hepatic Stellate Cells. Cell Mol Gastroenterol Hepatol. 2020;10(2):341-364.  DOI: 10.1016/j.jcmgh.2020.04.005

9.  Liu Z, Zhang Y, Graham S, Wang X, Cai D, Huang M, Pique-Regi R, Dong XC, Chen YE, Willer C, Liu W.   Causal relationships between NAFLD, T2D and obesity have implications for disease subphenotyping. J Hepatol. 2020 Aug;73(2):263-276.  DOI: 10.1016/j.jhep.2020.03.006

Faculty Research Team

19563-Dong, X

X C. Dong, PhD

Professor of Biochemistry & Molecular Biology

Read Bio

Hyeong-Geug Kim, PhD, MS, BS

Postdoctoral Fellow in Biochemistry & Molecular Biology

Read Bio

Additional Research Team Members

Other faculty lab team members include Yunjian Liu, MD; Ping Xu, PhD; Yang Zhang, PhD; and Xiaolin Zhong, MD.