Chung, Stephen Sum Man

鍾森文

Professor

e-mail: smchung@hkucc.hku.hk

Tel. 2819-9202

Senju International Cataract Research Award
Outstanding Researcher Award, 1998.

Molecular Physiology
Diabetic Complications

Research in our laboratory mainly focuses on the pathogenesis of diabetic complications, including cataract, retinopathy, neuropathy, nephropathy, and cardiovascular diseases. Although it is well establish that high blood glucose is the primary cause of these diseases, the mechanism is not clear. Several models had been proposed, including non-enzymatic glycation, abnormal activation of PKC, oxidative stress and polyol pathway. We use transgenic and gene knockout mouse models to study the role of polyol pathway in these diseases (see the last reference listed below for review). Aldose reductase (AR), the first and rate-limiting enzyme of the pathway, reduces glucose to sorbitol, which is then converted to fructose by sorbitol dehydrogenase (SDH). The increase in sorbitol, as well as decrease in NADPH and NAD⁺, the co-factors for AR and ADH, respectively, are thought to contribute to the toxic effects of glucose (see figure). We are currently investigating other deleterious effects of increased polyol pathway activities in diabetic animals. A better understanding of the mechanisms of glucose toxicity will help us develop better means to prevent various secondary diseases associated with diabetes.

REPRESENTATIVE PUBLICATIONS

Yang, J.Y., Tam, W.Y., Tam, S., Guo, H., Wu, X., Li, G., Chau, J.F., Klein, J.D., Chung, S.K., Sands, J.M. and Chung, S.S.M. (2006) Genetic restoration of aldose reductase to the collecting tubules restores maturation of the urine concentrating mechanism. Am. J. Physiol. Renal Physiol. 291, F186-F195.
Chau, J.F.L., Lee, K.M.K., Law, J.W.S., Chung, S.K. and Chung, S.S.M. (2005) Sodium/myo-inositol co-transporter-1 is essential for the development and function of the peripheral nerves. FASEB J. 19, 1887-89.
Wang, Y., Ko, B.C.B., Yang, J.Y., Lam, T.T.L. Zhang, J., Chung, S.K. and Chung, S.S.M. (2005) Transgenic mice expressing dominant negative OREBP in lens exhibited fiber cell elongation defect associated with increase DNA breaks J. Biol. Chem. 280, 19986-19991.
Lam, A.K.M., Ko, B.C.B., Tam, S., Morris, R., Yang, J.Y., Chung, S.K. and Chung, S.S.M. (2004) Osmotic response element binding protein (OREBP) is an essential regulator of urine concentrating mechanism. J. Biol. Chem. 279, 48048-54.
Chung, S.S.M. and Chung, S.K. (2003) Genetic analysis of aldose reductase in diabetic complications. Curr. Med. Chem. 10, 375-87.