王祥喜

中国科学院生物物理研究所

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  • 王祥喜
  • 研究员

王祥喜 博士 研究员 博士生导师

中国科学院生物物理研究所,中国科学院感染与免疫重点实验室,研究组长

研究方向:病毒入侵、复制与组装分子机制

电子邮件(E-mail) xiangxi(AT)ibp.ac.cn

电话(Tel) 010-64888806

邮政编码 100101

英文版个人网页

简历 & 研究组工作摘要

教育经历

2014年中国科学院生物物理研究所获得理学博士学位

2009年 四川大学生物技术专业获得理学学士学位

工作经历

2014.10 - 至今中国科学院生物物理研究所研究员

2014.09 - 2016.02 牛津大学访问学者

2014.07 - 2014.09 中国科学院生物物理研究所副研究员

代表性奖励

(1)贝时璋青年生物物理学家奖,2015

(2)青年人才托举工程,2015

(3)中国科学院青年研究员人才计划,2014

(4)吴瑞奖学金,2014

研究方向

运用低温冷冻电镜、病毒学、细胞生物学等技术方法,从事人类重大疾病直接相关的病毒完整颗粒及病毒与受体、病毒与抗体的超大分子复合物的精细三维结构和相关功能研究,揭示病毒入侵宿主细胞的分子机制和致病机理以及抗病毒药物研究。主要研究方向包括:1. 疱疹病毒的复制、组装和运输机制;2. 脑炎性黄病毒神经毒力的分子机制;3.小RNA病毒的入侵和组装机制及抗病毒药物研究。

1. 疱疹病毒的复制、组装和运输机制

疱疹病毒是在世界范围内广泛传播的一大类病毒,包含病毒的种类众多,能够感染包括人类在内的多种哺乳动物。疱疹病毒在感染人体后能够引发多种疾病,包括口腔和生殖器疱疹、水痘、带状疱疹,严重的甚至包括多种免疫系统疾病、脑炎以及癌症等。疱疹病毒有着独特的潜伏-再活化机制,疱疹病毒可以关闭其大部分活动状态的基因,只在特定的潜伏阶段打开特定的少数基因,并在合适的条件下恢复活性,重新进入增殖过程。这种潜伏-再活化机制使得疱疹病毒感染产生的疾病难以完全治愈,通常患者会终生携带病毒。同时疱疹病毒又是非常好的“融瘤”和“神经环路示踪”工具,目前已经进入临床应用。本课题组致力于理解疱疹病毒的复制、组装的动态过程,揭示疱疹病毒在宿主细胞的运输和潜伏与再激活分子机理,为有效防治疱疹病毒的感染和人类生命医学技术手段的提高提供理论基础。

2. 脑炎性黄病毒神经毒力的分子机制

黄病毒,是一类具有包膜的单股正链RNA病毒,主要是通过吸血的节肢动物(蚊、蜱、白蛉等) 进行传播的虫媒病毒,能够广泛引起人类很多重大传染性疾病,主要包括乙型脑炎病毒 (JEV)、森林脑炎病毒、登革热病毒、寨卡病毒和黄热病毒等。黄病毒科中有一大类病毒能够直接入侵脑部而引起的颅内急性炎症,即:病毒性脑炎。本课题组聚焦脑炎性黄病毒神经毒力的分子机制。

3. 小RNA病毒的入侵和组装机制及抗病毒药物研究

小RNA病毒是一类无包膜的单股正链RNA病毒,可引起人类和动物多种严重疾病,如:甲型肝炎、小儿麻痹症、口蹄疫、手足口病和普通感冒等。除了是众多疾病的主要病原,小RNA病毒也是研究病原(病毒)与宿主之间的关系、病毒的入侵和病毒基因组的释放等关键科学问题最好的模型之一。本课题组致力于揭示小RNA病毒入侵宿主细胞和病毒发生脱衣壳过程的动态分子机制,在此基础上靶向设计能够高效阻止病毒入侵过程的小分子抑制剂及稳定性高、免疫原性好的病毒样颗粒候选疫苗。

代表性论文( * Corresponding Authors, # First Authors ):

1. Shuai Yuan#, Jialing Wang#, Dongjie Zhu#, Nan Wang, QiangGao, Wenyuan Chen, Junzhi Wang*, Xinzheng Zhang*, Hongrong Liu*, ZiheRao*, Xiangxi Wang*, Cryo-EM structure of a Herpesvirus capsid at 3.1 ?, Science, 2018, 360 (6384): 48-58

2. Ling Zhu#*, Yao Sun#, Jinyan Fan#, Bin Zhu, Lei Cao, QiangGao, Yanjun Zhang*, Hongrong Liu, ZiheRao*, Xiangxi Wang*, Structures of Coxsackievirus A10 unveil the molecular mechanisms of receptor binding and viral uncoating, Nature Communications, 2018, 9: 4985

3. Jialing Wang#, Shuai Yuan#, Dongjie Zhu#, Hao Tang, Nan Wang, Wenyuan Chen, QiangGao, Yuhua Li, Junzhi Wang, Hongrong Liu*, Xinzheng Zhang*, ZiheRao*, Xiangxi Wang*, Structure of the herpes simplex virus type 2 C-capsid with capsid-vertex-specific component, Nature Communications, 2018, 9: 3668

4. XiaodiQiu#, Yingfeng Lei#, Pan Yang, QiangGao, Nan Wang, Lei Cao, Shuai Yuan, Xiaofang Huang, Yongqiang Deng, Wenyu Ma, Tianbing Ding, Fanglin Zhang, Xingan Wu, Junjie Hu, Shan-Lu Liu, Chengfeng Qin, Xiangxi Wang*, ZhikaiXu*, ZiheRao*, Structural basis for neutralization of Japanese encephalitis virus by two potent therapeutic antibodies, Nature Microbiology, 2018, 3: 287–294

5. YangaoHuo#*, Tao Li, Nan Wang, Qinghua Dong, Xiangxi Wang*, Tao Jiang*, Cryo-EM structure of Type III-A CRISPR effector complex, Cell Research, 2018, 28: 1195–1197

6. Ling Zhu#, KangweiXu#, Nan Wang#, Lei Cao, Junlan Wu, QiangGao, Elizabeth E. Fry, David I. Stuart, ZiheRao, Junzhi Wang, Xiangxi Wang*, Neutralization Mechanisms of Two Highly Potent Antibodies against Human Enterovirus 71, mBio, 2018, 9: e01013-18

7. Xiangxi Wang#,*, Ling Zhu#, Minghao Dang#, Zhongyu Hu#, QiangGao, Shuai Yuan, Yao Sun, Bo Zhang, JingshanRen, AbhayKotecha, Thomas S. Walter, Junzhi Wang*, Elizabeth E. Fry*, David I. Stuart*, ZiheRao*, Potent neutralization of hepatitis A virus reveals a receptor mimic mechanism and the receptor recognition site, ProcNatlAcadSci U S A, 2017, 114: 770~775

8. Xiangxi Wang#,*, Shi-Hua Li#, Ling Zhu#, Qing-Gong Nian#, Shuai Yuan, QiangGao, Zhongyu Hu, Qing Ye, Xiao-Feng Li, Dong-Yang Xie, Neil Shaw, Junzhi Wang, Thomas S. Walter, Juha T. Huiskonen, Elizabeth E. Fry, Cheng-Feng Qin*, David I. Stuart*, ZiheRao*, Near-atomic structure of Japanese encephalitis virus reveals critical determinants of virulence and stability, Nature Communications, 2017, 8: 14

9. Xuyuan Zhang#, Pan Yang#, Nan Wang, Jialong Zhang, Jingyun Li, HaoGuo, Xiangyun Yin, ZiheRao, Xiangxi Wang*, Liguo Zhang*, The binding of a monoclonal antibody to the apical region of SCARB2 blocks EV71 infection, Protein & Cell, 2017, 8: 590–600

10. Ling Zhu#, Xiangxi Wang#, JingshanRen, AbhayKotecha, Thomas S. Walter, Shuai Yuan, Teruo Yamashita, Tobias J. Tuthill, Elizabeth E. Fry, ZiheRao*, David I. Stuart*, Structure of human Aichi virus and implications for receptor binding, Nature Microbiology, 2016, 1: 16150

11. Xiangxi Wang#, JingshanRen#, QiangGao#, Zhongyu Hu, Yao Sun, Xuemei Li, David J. Rowlands, Weidong Yin, Junzhi Wang*, David I. Stuart*, ZiheRao*, Elizabeth E. Fry, Hepatitis A virus and the origins of picornaviruses, Nature, 2015, 517: 85-88

12. Ling Zhu#, Xiangxi Wang#, JingshanRen, Claudine Porta, Hannah Wenham, Jens-Ola Ekstr?m, AnushaPanjwani, Nick J. Knowles, AbhayKotecha, C. Alistair Siebert, A. Michael Lindberg, Elizabeth E. Fry, ZiheRao, Tobias J. Tuthill, David I. Stuart*, Structure of Ljungan virus provides insight into genome packaging of this picornavirus, Nature Communications, 2015, 6: 8316

13. Luigi De Colibus#, Xiangxi Wang#, AloysTijsma, Johan Neyts, John A. B. Spyrou, JingshanRen, Jonathan M. Grimes, Gerhard Puerstinger, Pieter Leyssen, Elizabeth E. Fry, ZiheRao*, David I. Stuart*, Structure Elucidation of Coxsackievirus A16 in Complex with GPP3 Informs a Systematic Review of Highly Potent Capsid Binders to Enteroviruses, PLoSPathog, 2015, 11: e1005165

14. JingshanRen#, Xiangxi Wang#, Ling Zhu#, Zhongyu Hu, QiangGao, Pan Yang, Xuemei Li, Junzhi Wang, XinliangShen, Elizabeth E. Fry, ZiheRao*, David I. Stuart*, Structures of Coxsackievirus A16 Capsids with Native Antigenicity: Implications for Particle Expansion, Receptor Binding, and Immunogenicity, Journal of Virology, 2015, 89: 10500-10511

15. Shuai Yuan#, Lei Cao, Hui Ling, Minghao Dang, Yao Sun, Xuyuan Zhang, Yutao Chen, LiguoZhang, Dan Su, Xiangxi Wang*, ZiheRao*, TIM-1 acts a dual-attachment receptor for Ebolavirus by interacting directly with viral GP and the PS on the viral envelope, Protein & Cell, 2015, 6: 814–824

16. Luigi De Colibus#, Xiangxi Wang#, John A B Spyrou, James Kelly, JingshanRen, Jonathan Grimes, Gerhard Puerstinger, Nicola Stonehouse, Thomas S Walter, Zhongyu Hu, Junzhi Wang, Xuemei Li, Wei Peng, David J Rowlands, Elizabeth E Fry, ZiheRao*, David I Stuart*, More-powerful virus inhibitors from structure-based analysis of HEV71 capsid-binding molecules, Nature Structural & Molecular Biology, 2014, 21: 282–288

17. Minghao Dang#, Xiangxi Wang#, Quan Wang, Yaxin Wang, Jianping Lin, Yuna Sun, Xuemei Li, Liguo Zhang, Zhiyong Lou, Junzhi Wang, ZiheRao*, Molecular mechanism of SCARB2-mediated attachment and uncoating of EV71, Protein & Cell, 2014, 5: 692–703

18. JingshanRen#, Xiangxi Wang#, Zhongyu Hu, QiangGao, Yao Sun, Xuemei Li, Claudine Porta, Thomas S. Walter, Robert J. Gilbert, Yuguang Zhao, Danny Axford, Mark Williams, Katherine McAuley, David J. Rowlands, Weidong Yin, Junzhi Wang*, David I. Stuart*, ZiheRao, Elizabeth E. Fry, Picornavirusuncoating intermediate captured in atomic detail, Nature Communications, 2013, 4: 1929

19. Yao Sun#, Xiangxi Wang#, Shuai Yuan, Minghao Dang, Xuemei Li, Xuejun C. Zhang, ZiheRao*, An open conformation determined by a structural switch for 2A protease from coxsackievirus A16, Protein & Cell, 2013, 4: 782–792

20. Xiangxi Wang#, Wei Peng#, JingshanRen#, Zhongyu Hu, JiweiXu, Zhiyong Lou, Xumei Li, Weidong Yin, XinliangShen, Claudine Porta, Thomas S Walter, Gwyndaf Evans, Danny Axford, Robin Owen, David J Rowlands, Junzhi Wang*, David I Stuart*, Elizabeth E Fry*, ZiheRao*, A sensor-adaptor mechanism for enterovirusuncoating from structures of EV71, Nature Structural & Molecular Biology, 2012, 19: 424–429

资料来源:王祥喜研究员,2019-02-12网页制作