H. Henry Dong, PhD
Associate Professor of Pediatrics
Dr. Dong is a member of the Cellular and Molecular Pathology Graduate Training Program.
Children's Hospital of Pittsburgh
Rangos Research Center, Room 6124
4401 Penn Avenue
Pittsburgh, PA 15244
Office Telephone: 412-692-6324
Lab Telephone: 412-692-6570
- PhD - Uppsala University, Sweden, 1995
Research InterestsDr. Dong is an associate professor in the Department of Pediatrics, University of Pittsburgh School of Medicine. Dr. Dong focuses on studies of the molecular basis that links insulin resistance to diabetic dyslipidemia in subjects with morbid obesity and type 2 diabetes. Insulin resistance is defined as a significantly diminished state of responsiveness of the body to normal plasma insulin concentrations. To overcome insulin resistance in peripheral tissue, the pancreatic beta cells are called upon to produce more insulin via a compensatory mechanism, which over time can lead to beta-cell failure and overt diabetes. Despite tremendous efforts to elucidate the molecular basis of insulin resistance, a unifying idea to account for the pathophysiology of insulin resistance in obesity and type 2 diabetes is still lacking. Using transgenic, gene knockout and gene transfer approaches, Dr. Dong’s lab focuses on the characterization of forkhead transcription factors in glucose and lipid metabolism to understand how insulin resistance perturbs carbohydrate metabolism, contributing to the development of diabetic dyslipidemia. These studies are expected to gain insight into the molecular events that link insulin resistance to metabolic abnormalities, providing a knowledge base for the development of small molecule drugs for better clinical management of diabetic dyslipidemia in obesity and type 2 diabetes.
A second focus of Dr. Dong’s research is on the development of insulin replacement therapy for type 1 diabetes. Type 1 diabetes is caused by the lack of insulin production in the pancreas. Insulin gene therapy is being developed as an alternative insulin replacement therapy, as it offers great potential for achieving long-term blood glucose control without eliciting immune rejection. The insulin gene is delivered through a gene vehicle to the liver, such that insulin will be produced in liver cells and released into the blood stream. Dr. Dong’s research has provided proof-of-principle that insulin production at a basal level in the liver is sufficient to prevent urine ketone and relieve diabetes symptoms in diabetic animals. To improve this procedure, Dr. Dong works to control insulin production in the liver to achieve insulin release in a glucose-dependent manner. In this autoregulated system, insulin production will be stimulated when blood sugar is high and suppressed when blood sugar is low. This highly regulated system is expected to improve blood sugar control without the need of daily insulin injection. Dr. Dong’s team is conducting preclinical trials of this insulin gene therapy protocol for its safety and efficacy in blood sugar control in diabetic animals.
Awards and HonorsAmerican Diabetes Association Career Development Award, 2004-2010
Selected PublicationsView Dr. Dong's publications on PubMed
Cifarelli V, Lee S, Hyun Kim D, Zhang T, Kamagate A, Slusher S, Bertera S, Luppi P, Trucco M, Dong HH. FOXO1 mediates the autocrine effect of endothelin-1 on endothelial cell survival. Mol Endocrinol. 2012 May 8. [Epub ahead of print]
Kim DH, Perdomo G, Zhang T, Slusher S, Lee S, Phillip BE, Fan Y, Giannoukakis N, Gramignoli R, Strom S, Ringquist S, Dong HH. FoxO6 integrates insulin signaling with gluconeogenesis in the liver. Diabetes. 60:2763–2774. 2011
Kamagate A, Kim DH, Zhang T, Slusher S, Gramignoli R, Strom SC, Bertera S, Ringquist S, Dong HH. FoxO1 links hepatic insulin action to endoplasmic reticulum stress. Endocrinology 151(8):3521-35. 2010
Su D, Coudriet GM, Kim DH, Lu Y, Perdomo G, Qu S, Slusher S, Tse HM, Piganelli J, Giannoukakis N, Zhang J and Dong HH. FoxO1 Links Insulin Resistance to Proinflammatory Cytokine IL-1beta Production in Macrophages. Diabetes. 58. 2624-2633. 2009
*Featured in Scientific American. Melinda Wenner. Does Inflammation Trigger Insulin Resistance and Diabetes? Scientific American. Dec. Vol. 301. No 6. Pages 24-26. 2009.
Kamagate A., Qu S., Perdomo G., Kim DH., Slusher S. Meseck, M and Dong HH. FoxO1 mediates insulin-dependent regulation of hepatic VLDL production. J. Clin. Invest. 118:2347-2364. 2008.
*Commentary: Sparks JD, Sparks CE. Overindulgence and metabolic syndrome: is FoxO1 a missing link? J Clin Invest. 2008 Jun;118(6):2012-5.
Su D., Zhang N., He J., Qu S., Slusher S., Bottino R., Bertera S., Bromberg J. and Dong HH. Angiopoietin-1 production in islets improves islet engraftment and protects islets from cytokine-induced apoptosis. Diabetes. 56:2274-83. 2007.
Qu S., Altomonte J., Perdomo G., He J., Fan Y., Kamagate A., Meseck M. and Dong HH. Aberrant FoxO1 function is associated with impaired hepatic metabolism. Endocrinology. 147:5641-5652. 2006.
Altomonte, J., Cong, L., Richter, A., Harbaran, S., Xu, J., Nakae, J., Meseck, M., and Dong HH. (2004). Foxo1 mediates insulin action on apoC-III and triglyceride metabolism. J. Clin. Invest. 114:1493-1503.
Zhang, N., Richter, A., Suriawinata, J., Harbaran, S., Altomonte, J., Cong, L., Zhang, H., Song, K., Meseck, M., Bromberg, J., and Dong HH. (2004). Elevated VEGF production in islets improves islet graft vascularization. Diabetes. 53:963-970.