Cheng, Y.-S. Edmond 鄭義循
EDUCATION AND POSITIONS HELD:
- Ph.D., Biological Sciences, Purdue University (1976)
- Postdoctoral Fellow, Cold Spring Harbor Laboratory ( 1977-1979)
- Instructor, Harvard University (1979-1980)
- Member of Research Staff , E. I. Dupont & Co. (1980-1990)
- Senior Research Virologist, Dupont Merck pharmaceutical Co. (1990-1994)
- Senior Director Biology, Fuji ImmunoPharmaceutical Corp. (1994-1997)
- Senior Director Biochemistry, Shionogi BioResearch Corp. (1997-2001)
- President, NeutraPharmaceutical Corp. (2001-2002)
- Director of Pharmacology, Gryphon Therapeutics (2002-2003)
- Senior Research Specialist, Genomics Research Center, Academia Sinica, 2003-present
EXPERTISE / SPECIALTY / ACHIEVEMENT:
I went through two different research tracks before I joined Academia Sinica. When I was working at E. I. Dupont & Co. and Dupont Merck Pharmaceutical Co., I was interested in anti-viral mechanisms. In my interferon mechanistic study, I identified two novel interferon-induced guanylate binding proteins (GBP) from both human and murine cells. These proteins were purified and the cDNAs cloned and characterized. Subsequent studies in other laboratories defined the antiviral functions of GBP and the related interferon regulatory elements. I then started a research interest in viral proteases and their inhibitors. My earlier studies in HIV-1 and HIV-2 proteases were highlighted in the construction of the novel one-chain dimmers of these proteases. These studies led to the structural studies of these proteins and their inhibitor interactions. In addition, my research activities of the HIV-1 protease produced the first HIV protease animal model in a transgenic mice and the first demonstration that drug resistant HIV mutants could be readily induced from protease inhibitor-treated HIV populations. My research activities during my subsequent appointments were more diversified, focusing on drug discovery, lead development, and some product development studies. Throughout that period, my research activities included high throughput screening for drug lead discovery, lead optimizations, and preclinical pharmacology studies. At GRC, my interesting is to help the group verify drug targets using RNAi silencing technologies, develop assay protocols and identify drug leads by high throughput screening of compound libraries.
在加入中央研究院之前，我經歷了兩段非常不同的研究生涯。當我在E. I. Dupont & Co. 及 Dupont Merck Pharmaceutical 工作時我的研究重點是在對於抗病毒機制的了解。我發現干擾素可以促進一種新的蛋白，GBP，的合成。我在GBP及其 mRNA上的研究導致後人對干擾素引導的控制機理之了解。之後，我開始了對HIV 蛋白水解酵素及其抑制劑的興趣。我的研究開始於我對HIV-1蛋白水解酵素的特殊設計：one-chain dimmer。除了對蛋白結構及其與抑制劑的結合體的成就之外，我也同時研發出第一個動物模型來探測HIV-1蛋白水解酵素的抑制劑，同時我的研究又證明 對蛋白水解酵素抑制劑有抗藥性的HIV是很容易就會在用藥的過程中產生出來。我最近幾年所做的研究工作是比較多元性，著重於新藥的開發及產品的發展，在這 段期間我的研究工作包括高速藥物篩選，藥效改善，以及藥劑學有關的研發。我目前的研發的方向是: (1)協助基因体中心借由RNAi對基因表達的抑制來確認開發新藥之標的, (2)開發因應的測試方法並用高速高效的藥物篩選法由藥庫中找出先導藥物的結構。
- Wen WH, Lin M, Su CY, Wang SY, Cheng YS, Fang JM, Wong CH, 2009, “Synergistic effect of zanamivir-porphyrin conjugates on inhibition of neuraminidase and inactivation of influenza virus.”, Journal of medicinal chemistry, 52(15), 4903-4910. (SCI)
- Su CY, Wang SY, Shie JJ, Jeng KS, Temperton NJ, Fang JM, Wong CH, Cheng YS, 2008, “In vitro evaluation of neuraminidase inhibitors using the neuraminidase-dependent release assay of hemagglutinin-pseudotyped viruses.”, Antiviral research, 79(3), 199-205. (SCI)
- M. J. Otto, S. Garber, D. L. Winslow, C. D. Reid, P. Aldrich, P. K. Jadhav, C. E. Patterson, C. N. Hodge and Y.S.E. Cheng, 1993, “In vitro isolation and identification of human immunodeficiency virus (HIV) variants with reduced sensitivity to C-2 symmetrical inhibitors of HIV type 1 protease”, Proc Natl Acad Sci U S A, 90, 7543-7547.
- Y.S.E. Cheng, C. E. Patterson and P. Staeheli, 1991, “Interferon-induced guanylate-binding proteins lack an N(T)KXD consensus motif and bind GMP in addition to GDP and GTP”, Mol Cell Biol, 11, 4717-4725. (SCI)
- Y.S.E. Cheng, F. H. Yin, S. Foundling, D. Blomstrom and C. A. Kettner, 1990, “Stability and activity of human immunodeficiency virus protease: comparison of the natural dimer with a homologous, single-chain tethered dimer”, Proc Natl Acad Sci U S A, 87, 9660-9664.
- Y.S.E. Cheng, R. J. Colonno and F. H. Yin, 1983, “Interferon induction of fibroblast proteins with guanylate binding activity”, J Biol Chem, 258, 7746-7750. (SCI)