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

Dr. Charlie Dong’s 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.

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

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

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

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

Agency: IUSM & Showalter Trust Funds

Goal: To enhance faculty research and career development.

Amount: $75,000

Role: PI

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

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

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

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. 2017 (in press).
  2. Xiong X, Zhang C, Zhang Y, Fan R, Qian X, Dong XC. Fabp4-Cre-mediated Sirt6 deletion impairs adipose tissue function and metabolic homeostasis in mice. J Endocrinol. 2017 Apr 6. pii: JOE-17-0033.
  3. Pan X, Zhang Y, Kim HG, Liangpunsakul S, Dong XC. FOXO transcription factors protect against the diet-induced fatty liver disease. Sci Rep. 2017 Mar 16; 7:44597.
  4. Xiong X, Wang G, Tao R, Wu P, Kono T, Li K, Ding WX, Tong, X, Tersey SA, Harris RA, Mirmira RG, Evans-Molina C, Dong XC. Sirtuin 6 regulates glucose-stimulated insulin secretion in mouse pancreatic beta cells. Diabetologia 2016 Jan;59(1):151-60.
  5. Tao R, Xiong X, Liangpunsakul S, Dong XC. Sestrin 3 protein enhances hepatic insulin sensitivity by direct activation of the mTORC2-Akt signaling. Diabetes 2015 Apr; 64(4): 1211-23.

Faculty Research Team

X C. Dong, PhD

X C. Dong, PhD

Associate Professor of Biochemistry & Molecular Biology
Menghao Huang, PhD

Menghao Huang, PhD

Postdoctoral Fellow in Medicine
Hyeong-Geug Kim, PHD

Hyeong-Geug Kim, PHD

Postdoctoral Fellow in Biochemistry & Molecular Biology

Additional Research Team Members

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