陳暢，博士，研究員，博士生導師、黨委委員，計算與系統生物學研究中心副主任。國家重大科學研究計畫(蛋白質研究計畫“973”)項目首席科學家。南京大學客座教授。
基本介紹
- 中文名：陳暢
- 職業：教師
- 畢業院校：南開大學
- 學位/學歷：博士
- 專業方向：細胞氧化還原調控的分子機理
- 職務：中科院計算與系統生物學研究中心副主任
人物經歷,研究方向,主要貢獻,主要成果,發明專利,
人物經歷
1986-1990南開大學，理學學士學位；
1990-1993北京師範大學，理學碩士學位；
1993-1996北京大學，理學博士學位，同年到中科院生物物理研究所任助研；
1996-1998中國科學院生物物理研究所，助理研究員；
1998-2000中國科學院生物物理研究所副研究員,獲英國皇家學會K. C. Wong Fellowship及受英國皇家學會Joint project資助在英國國立食品研究所（Institute of Food Research, UK）訪問學者；
2000-至今 中國科學院生物物理研究所創新研究課題組長(PI)，2004年晉升研究員；
2004.12-2005.03 英國劍橋MRC（Medical Research Council）訪問學者。
1998-2000年獲英國皇家學會資助到英國國立食品研究所（Institute of Food Research, UK）合作研究。
2000年5月回到生物物理研究所組任創新研究組長（獨立PI）。
現任中國生物物理學會理事，副秘書長；中國生物物理學會自由基生物學與醫學專業委員會副主任；亞洲國際自由基學會委員；中國生化與分子生物學學會理事；北京生化與分子生物學學會理事；《生物物理學報》副主編；《生物化學與生物物理進展》編委；國際學術期刊“The Open Nitric Oxide Journal”編委。
研究方向
主要從事細胞氧化還原調控的分子機理研究。
細胞的氧化還原調控失衡是導致亞健康、衰老、神經退行性疾病、炎症、腫瘤、糖尿病等的重要因素，因此，細胞氧化還原調控的分子機理研究具有重要理論和實際意義。
近年研究發現：機體在應激條件下產生的一氧化氮等活性氮及活性氧小分子通過對蛋白質中氧化還原敏感的半胱氨酸巰基進行修飾，影響蛋白的結構、活性、定位、組裝和降解，從而調控蛋白的功能和細胞信號傳導，最終在生理和病理過程中發揮作用。這種修飾稱為氧化還原依賴的蛋白翻譯後修飾（Redox based post-translational modification of protein），包括：亞硝基化修飾(-SNO)、不同程度的氧化修飾（-S-S-; -S-OH; -SO3）、谷胱甘肽化修飾(-SSG)等，與磷酸化修飾一樣，是兩種進化上高度保守的蛋白翻譯後修飾之一。我們致力於揭示生命活動中這些小分子和大分子的對白，揭示氧化還原依賴的蛋白質巰基翻譯後修飾在細胞命運和疾病發生中的作用。重點研究一氧化氮生物活性及其對蛋白巰基的亞硝基化修飾在細胞信號轉導中的作用。主要有以下三個方面。
1、蛋白質巰基修飾的功能和方法研究。
2、氧化應激/氮應激（oxidative stress/nitrosative stress）在疾病發生髮展中的作用機理以及天然產物/中醫藥的調控和套用。
3、肌醇磷脂4位激酶phosphatidylinositol 4-kinase type IIα (PI4KIIα)和一氧化氮代謝調控蛋白S-nitrosoglutathione reductase (GSNOR)的功能與分子機制研究。
主要貢獻
主持國家自然科學基金重點項目1項，面上項目4項。作為首席科學家主持國家重大科學研究計畫（蛋白質研究）1項，作為課題負責人承擔國家重大研究計畫一項。主持“863”計畫探索項目1項，主持中科院青年創新基金和創新青年科學家小組課題各1項。在Free Radical Biol Med, J Cell Sci, Nucleic Acids Res, Oncogene等發表SCI論文39篇,申請國家發明專利兩項，撰寫兩本書籍章節。
主要成果
揭示了亞硝基化修飾在調控蛋白核質轉運中的作用，發現一氧化氮通過亞硝基化修飾調控核輸出受體CRM1的功能，擴展了對核輸出調控機制和一氧化氮生物學功能的認識。揭示了亞硝基化－泛素化－SUMO化三種蛋白質翻譯後修飾的相互調控，本工作提示：調控其它蛋白質翻譯後修飾可能是巰基亞硝基化修飾發揮作用的重要途徑。
揭示了NO代謝調控對學習記憶的調控作用，率先提出NO生物活性受合成和代謝雙調控的觀點，部分揭示了NO代謝酶GSNOR在神經系統的生理意義。
發展定量高通量亞硝基化檢測方法解決了內源亞硝基化檢測難題；發現和排除了亞硝基化檢測中的假陽性信號，引起本領域的廣泛關注；尤其是我們建立了不可逆親和素標記方法（IBP）, 是目前唯一能排除分子間二硫鍵干擾及-SSH巰基修飾的特異亞硝基化檢測方法。
發現新的腫瘤生長調控蛋白Phosphatidylinositol 4-kinase type IIα，PI4KIIα. 該蛋白α亞型特異地調控HER-2/PI3K，ERK1/2 信號通路，調控HIF-1α蛋白的合成，影響了HIF-1下游促血管生成因子VEGF，iNOS等蛋白的表達，影響內皮細胞的成管及遷移能力進而影響血管新生，最終調控腫瘤的生長目前我們已構建PI4KIIα轉基因鼠，正在進行PI4KIIα在腫瘤細胞轉移方面的機理研究。
Biography & Introduction
Chang CHEN,PhD, Professor of Institute of Biophysics, ChineseAcademy of Sciences
1996, Ph.D. of Peking University
1998, associate professor of Institute of Biophysics, CAS;
1998-2000, visiting scientist in Institute of Food Research, UK; 2000- PI, Institute of Biophysics (2004, full professor), CAS.
Professional activities:
? Vice-president of the Society of Free Radical Biology and Medicine, China.
? Associated editor of the journal “Acta Biophysica Sinica” (the offical journal of the Biophysics Society of China).
? Editorial board member of “The Open Nitric Oxide Journal”.
? Editorial board member of “Progress in Biochemistry and Biophysics”.
Research interests:
Bioactivity of nitric oxide and redox-based protein thiol modification; Natural product development;Functional study of phosphatidylinositol 4-kinase type IIα (PI4KIIα) andS-nitrosoglutathione reductase (GSNOR) in transgenic mice.
NO, as a putative messenger, is implicated in physiological and pathological processes. Apart from the well-known cGMP-dependent signaling pathway of NO, there is also a cGMP-independent pathway that involves S- nitrosylation. S- nitrosylation is a ubiquitous redox-related modification of cysteine thiols by nitric oxide, which transduces the bioactivity of NO. The mechanism and the cellular effects of this redox-based post-translational modification of proteins are not well understood. Our approach to understanding this process involves three aspects:
1) Investigation of the effects of NO on the properties of proteins, such as folding kinetics, stability, enzyme activity and protein-protein interactions, complex assembling. This part of the work provides a basis for the study of the cellular effects.
2) We are interested in investigating how SNO affects intracellular events, such as protein localization, protein-protein interactions, and how NO and SNO affect the apoptosis and differentiation cascade. We are also screening natural products for activity as anti-oxidative/nitrosative stress agents.
3) Investigation of the effects of NO and SNO at the level of the whole organism, such as in memory, diseases (diabetes, cancer, neurodegenerative diseases).
As the chief scientist, Prof. Chen has been awarded several research grants, including from the National Basic Research Program of China (or 973 Program), the National High Technology Research and Development Program (863 Program), and the National Natural Science Foundation of China (NSFC), and the Yong scientist group project of Chinese Academy of Sciences, and the Chinese Academy of Sciences Knowledge Innovation Project.
Selected Publications(*as the corresponding author, total =39)
1. Q. L. Hou, H. Q. Jiang, X. Zhang, C. Guo, B. Huang, P. Wang, T. P. Wang, K. Y. Wu; J. Li, Z. F. Gong; L. B. Du, Y. Liu, L. Liu, and Chang Chen*.Nitric oxide metabolism controlled by formaldehyde dehydrogenase (fdh, homolog of mammalian GSNOR) plays a crucial role in visual pattern memory in Drosophila. Nitric Oxide: Biology and Chemistry(2011) 24, 17-24.
2. X. Zhang, B. Huang, X. Zhou, andChang Chen*.Quantitative proteomic analysis of S-nitrosated proteins in diabetic mouse liver with ICAT switch method.Protein & Cell(2010) 1(7), 675-87.
3. B. Huang and Chang Chen*.Detection of protein S-nitrosation using irreversible biotinylation procedures (IBP). Free Radic. Biol. Med. (2010) 49, 447–456.
4. X. Zhou, P. Han, J. Li, X. Zhang, B. Huang, and Chang Chen*.ESNOQ, proteomic quantification of endogenous S-nitrosation. PLoS ONE(2010) 5(4): e10015. doi:10.1371/journal.pone.0010015.
5. J. M. Li, Y. Lu, J. H. Zhang, H. Kang, Z. H. Qin,and Chang Chen*. PI4KIIα is a novel regulator of tumor growth via its action on angiogenesis and HIF-1α regulation. Oncogene(2010) 29, 2550-2559.
6. J. Zhuang, T. X. Jiang, D. Lu, Y. T. Luo, C. G. Zheng, J. Feng, D. L. Yang, Chang Chenand X. Y. Yan. NADPH oxidase 4 mediates reactive oxygen species induction of CD146 dimerization in VEGF signal transduction. Free Radic. Biol. Med.(2010) 49, 227-236.
7. P. Wang, G. H. Liu, K. Y. Wu, J. Qu, B. Huang, X. Zhang, X. Zhou, L. Gerace, and Chang Chen*.Repression of classical nuclear export by S-nitrosylation of CRM1.J. Cell Sci.(2009) 122, 3772-3779.
8. S. J. Duan, L. Wan,W. J. Fu, H. Pan, Q. Ding, and Chang Chen, P. W. Han, X. Y. Zhu, L. Y. Du, H. X. Liu, Y. X. Chen, X. M. Liu, X. T. Yan, M. H. Deng, and M. P. Qian. Nonlinear cooperation of p53-ING1-induced bax expression and protein S-nitrosylation in GSNO-induced thymocyte apoptosis: a quantitative approach with cross-platform validation. Apoptosis(2009) 14(2), 236-45.
9. P. W. Han, X. Zhou, B. Huang, X. Zhang, and Chang Chen*，On-gel fluorescent visualization and the site identification of S-nitrosylated proteins. Anal. Biochem.(2008) 377, 150-155.
10. P. W. Han and Chang Chen*.Detergent-free biotin switch combined with LC-MS/MS in analysis of S-nitrosylated proteins. Rapid Commun. Mass Spectrom. (2008) 22(8), 1137-1145.
11. S. J. Duan and Chang Chen*. S-nitrosylation/denitrosylation and apoptosis of immune cells. Cell. Mol. Immunol.(2007) 4 (5), 353－358.
12. J. Qu, G.-H. Liu, K. Y. Wu, P. W. Han, P. Wang, J. M. Li, X. Zhang, and Chang Chen*. Nitric oxide destabilizes Pias3 and regulates sumoylation. PLoS ONE(2007) 2(10): e1085. doi:10.1371/ Journal.pone.0001085.
13. J. Qu., G.-H. Liu, B. Huang, and Chang Chen*.Nitric oxide controls nuclear export of APE1/Ref-1 through S-nitrosation of cysteines 93 and 310. Nucleic Acids Res. (2007) 35, 2522-2532.
14. J. He, T. P. Wang, P. Wang, P. W. Han, and Chang Chen*,A novel mechanism underlying the susceptibility of neuronal cells to nitric oxide: the occurrence and regulation of protein S-nitrosylation is the checkpoint. J. Neurochem.(2007) 102, 1863–1874.
15. B. Huang and Chang Chen*.An ascorbate-dependent artifact that interferes with the interpretation of the biotin switch assay. Free Radic. Biol. Med. (2006) 41, 562–567.
16. J. He, H. J. Kang, F. Yan, andChang Chen*.The endoplasmic reticulum-related events in S-nitrosoglutathione -induced neurotoxicity in cerebellar granule cells.Brain Res.(2004) 1015, 25-33.
17. B. Huang, J. S. Zhang, J. W. Hou, and Chang Chen*.Free radical scavenging efficiency of nano-Se in vitro. Free Radic. Biol. Med.(2003) 35(7), 805-813.
18. Taotao Wei, Chang Chen,Jingwu Hou, Wenjuan Xin and Akitane Mori. Nitric oxide induces oxidative stress and apoptosis in neuronal cells. Biochimica et Biophysica Acta,Mol. Cell Res.(2000)1498, 72-79.
19. Chang Chen, H. R. Tang, L. Sutcliffe, and P. Belton, Green tea polyphenols scavenge 1,1-dipenyl-2- picryl-hydrazyl free radicals in the bilayer of liposomes- Direct evidence from ESR studies. J. Agric.Food Chem.(2000) 8, 5710-5714.
20. Chang Chen, T. Wei, Z. H. Gao, B. Zhao, J. W. Hou, H. Xu, W. J. Xin, and L. Packer. Different effects of the constituents of EGb761 on apoptosis in rat cerebellar granule cells induced by hydroxyl radicals, Biochem. Mol. Biol. Int.(IUBMB Life) (1999) 47, 397-405.
發明專利
1. 特異檢測蛋白質或多肽半胱氨酸巰基修飾的方法及其用途，申請號為200910084155.7
2. 肌醇磷脂4位激酶二型α亞型PI4KIIα的套用，申請號為200810104272.0
