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Professor Chung joined The University of Hong Kong in 1991 and brought with her to Hong Kong the transgenic and gene knockout mouse technologies, and she used these technologies to investigate the metabolic stress associated with diabetes, particularly, the role of polyol pathway in the pathogenesis of diabetic complications. The polyol pathway consists of two enzymes, the first and rate-limiting enzyme aldose reductase (AR) reduces glucose to sorbitol, and sorbitol dehydrogenase (SDH), converts sorbitol to fructose. Using transgenic techniques she (in collaboration with Prof. Stephen Chung) showed that increased expression of AR in the lens made mice susceptible to develop diabetic cataract. By using SDH null mutant mice, she discovered that the sorbitol accumulation is the key culprit in development of in diabetic neuropathy. Later, she showed that increased expression of AR in the mouse nerves exacerbates the development of diabetic neuropathy. She also generated AR gene knockout mice, which developed mild diabetes insipidus. Using the double mutant mice with deletion of AR and SDH, she and her colleagues demonstrated that polyol pathway plays a key role in the development of various diabetic complications, including retinopathy, cardio- and cerebro-vascular diseases, such as heart attack and stroke. She worked with the pharmaceutical companies, such as Pfizer, USA and Sanwa, Japan to further develop use of AR inhibitors in diabetic and ischemic/reperfusion injuries to the peripheral nerve, retina and brain which lead to patents. She has also created transgenic mice with over-expression of endothelin-1 (ET-1) in endothelial cells or astrocytes, or ET-1 KO mice and demonstrated that ET-1 also plays an important role in cardio- and cerebro-vascular function, and astrocyte biology.
Prof. Chung has been continuing with the basic understanding of the regulation of AR by deleting the transcription factor, osmotic responsive element binding protein, OREBP/NFAT5, which regulate not only AR but also many important genes, such as HSP70, ion and water channels, transporters including sodium myoinositolcotransporter (SMIT). Deletion of NFAT5 leads to embryonic lethality with cardiac defect in homozygous KO mice, and more likely to develop ischemic stroke injury in heterozygous KO mice. The deletion of osmoregulatory gene, such as SMIT, lead to inability of cranial nerves to send out the cranial nerves during embryonic age leading to death due to inability to breath. Recently she is interested in GAP and GEF proteins, such as Deleted in Liver Cancer (DLC2) and Exchange Protein Activated by cAMP (Epac), which regulate RhoA or Rap1 and 2 activities, respectively. They determined that deletion of DLC2 leads to more inflammatory pain and diabetic neuropathy in mice. Deletion of Epac1 leads to metabolic syndrome with beta cell defect. Currently, these mouse models are being actively phenotype (including microarray and proteomics) to determine whether these genes are important in diabetes and its complications in various tissues, which are becoming a major health concern worldwide.
Prof. Chung is also actively participating in group research program, such as Area of Excellence, Theme-based Research Program and State Key Laboratory. She is involved in screening many potential compounds derived from traditional Chinese medicine with neuroprotective agents, which also lead to innovative discovery. Prof. Chung has provided my expertise in transgenic and knockout mice, and cryopreservation to other HKU and overseas members. We have provided our genetically manipulated mouse models to other researchers globally, including HK, China, USA, Korea and Japan.