陈畅研究员 Prof. Chang Chen
简介：
1990年毕业于南开大学，获理学学士学位；1993年毕业于北京师范大学，获理学硕士学位；1996年毕业于北京大学，获得理学博士学位，之后到中科院生物物理研究所工作。1998-2000年获英国皇家学会K.C.Wong Fellowship及英国皇家学会 Joint project资助,到英国国立食品研究所（Institute of Food Research, UK）进行合作研究。2000年5月回到生物物理研究所组建独立课题组。2004年12月－2005年3月到英国剑桥MRC (Medical Research Council)访问研究。现任中国科学院生物物理研究所创新研究组长、研究员、博士生导师、党委委员，计算与系统生物学研究中心副主任。国家重大科学研究计划
“重要功能膜蛋白的功能与结构研究”首席科学家。主持国家自然科学基金项目4项，国家海洋“863”计划探索项目1项，中国科学院青年科学家小组项目1项, 参加“973计划”1项。多次参加国际会议并作邀请报告，大会邀请报告一次。中国生物物理学会理事、副秘书长，自由基生物学和自由基医学专业委员会副主任，《生物化学与生物物理进展》编委，《生物物理学报》编委。国际学术期刊“The
Open Nitric Oxide Journal”编委。
研究组工作摘要：
主要研究方向: 细胞的氧化还原调控失衡与衰老、神经退行性疾病、炎症、糖尿病等都密切相关，其分子机制有待阐明。近年研究发现：机体在应激条件下产生的一氧化氮等活性氮及活性氧小分子通过对蛋白质中氧化还原敏感的半胱氨酸巯基进行修饰，影响蛋白的结构、活性、定位、组装和降解，从而调控蛋白的功能和细胞信号传导，最终在生理和病理过程中发挥作用。这种修饰称为氧化还原依赖的蛋白翻译后修饰。与磷酸化修饰一样，是两种进化上高度保守的蛋白翻译后修饰之一。我们致力于揭示生命活动中这种小分子和大分子的对白，即揭示细胞氧化还原调控的分子机制:氧化还原依赖的蛋白质翻译后修饰在细胞命运和疾病发生中的作用。重点研究一氧化氮对蛋白巯基的亚硝基化修饰及作用。
近期（2006-2007）主要工作和进展
1．致力于蛋白质巯基亚硝基化方法学的原始创新: 发现了维生素C在亚硝基化检测过程中引起假阳性信号；解决了高通量检测蛋白亚硝基化方法中表面活性剂对质谱的干扰和实验重复性差的问题；创建了蛋白亚硝基化的胶内快速直接可见检测方法;已建立高通量定量组学检测内源亚硝基化方法。
2．发现一氧化氮引起的蛋白质亚硝基化修饰失衡在细胞死亡中的关键作用，并首次阐述了蛋白质亚硝基化修饰与细胞氧化还原状态的定量依赖关系。
3．发现一氧化氮通过蛋白亚硝基化修饰诱导核酸内切酶APE1-REF1核输出，首次揭示了一氧化氮通过蛋白亚硝基化修饰特异机制实现对细胞蛋白核输入和核输出系统的调控。一氧化氮通过蛋白质巯基亚硝基化修饰调控SUMO修饰E3连接酶PIAS3稳定性，首次揭示了蛋白亚硝基化修饰、泛素化修饰及SUMO化修饰三种翻译后修饰的相互作用。
4．在研究单个蛋白亚硝基化对其功能调控的基础上，结合本课题组建立的蛋白亚硝基化修饰的定量组学方法和系统生物学思想，进行多靶点蛋白亚硝基化修饰作用网络的分析和动态变化研究。
英文摘要：
1996, Ph.D. of Peking Univ; 1998, associate professor of Institute of Biophysics; 1998-2000, visiting scientist in Institute of Food Research, UK; 2000- PI, Institute of Biophysics (2004, professor)
Research interests: The mechanism and the cellular effects of the redox-based post-translational modification of proteins, particularly on the S-nitrosylation of proteins induced by nitric oxide.
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-S- nitrosylation 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"), 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.
2006-2007代表性成果：
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Peiwei Han, Chang Chen*, Detergent-free biotin switch combined with LC-MS/MS in analysis of S-nitrosylated proteins. Rapid Communications in Mass Spectrometry , 2007(In press)
Jing Qu, Guang-Hui Liu, Kaiyuan Wu, Peiwei Han, Peng Wang, Jiangmei Li, Xu Zhang, Chang Chen*, Nitric Oxide Destabilizes Pias3 and Regulates Sumoylation. PLoS ONE, 2007, 2(10): e1085. doi:10.1371/journal.pone.0001085
Jing Qu, Guang-Hui Liu, Bo Huang, Chang Chen*, Nitric oxide controls nuclear export of APE1/Ref-1 through S-nitrosation of Cysteines 93 and 310. Nucleic Acids Research, 2007, 35:2522-2532
Jie He, Tiepeng Wang, Peng Wang, Peiwei Han, 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. Journal of Neurochemistry, 2007, 102, 1863-1874
Bo Huang, Chang Chen*, An ascorbate-dependent artifact that interferes with the interpretation of the biotin switch assay. Free Radical Biology & Medicine,
2006, 41, 562-567
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电子邮件(E-mail ) |
changchen(AT)moon.ibp.ac.cn（请将(AT)替换为@，防止垃圾邮件） |
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电话(Tel)
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010-64888406 |
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房间号（Room No.) |
2708 |
