成就
简介
2008年2月,已成为美国普林斯顿大学终身讲席教授的施一公,毅然辞职回到母校清华大学,在海外华人界引起施一公
施一公
了不小的震动。美国国立健康研究院研究室主任、国际知名神经科学家鲁白说:“他是海外华人归国的典范和榜样”。面对这些溢美之词,施一公教授显得很平静,他说:“我希望能够通过自己的努力,为改善和改进国家的教育体制和科技体制做些努力,能培养一批人才,为国家的发展和社会的进步做出一些贡献。”
在普林斯顿大学,他运用结构生物学、生物物理和生物化学手段,研究癌症发生和细胞凋亡的分子机制。迄今为止,他在国际权威学术杂志发表学术论文百余篇,其中作为通讯作者在《细胞》发表11篇、《自然》发表7篇、《科学》发表3篇。这些工作系统地揭示了哺乳动物、果蝇和线虫中细胞凋亡通路的分子机理,已有若干研究成果申请专利,用于治疗癌症的药物研发。
因在细胞凋亡和TGF-信号传导等领域的杰出工作,2003年他被国际蛋白质学会授予鄂文西格青年科学家奖,是该奖项设立以来第一位获此殊荣的华裔学者。2005年,当选华人生物学家协会会长。
回国后,是长江学者讲座教授,国家杰出青年基金获得者,“千人计划”首批国家特聘专家。[1]
美国院士
美国科学院当地时间2013年4月30日消息,清华大学施一公教授当选2013年该院外籍院士。此前2013年4月25日,他还当选美国人文与科学学院外籍院士。耶鲁大学终身冠名教授邓兴旺和陈雪梅、杨薇等三名华裔美籍科学家,当选美国科学院新科院士。
编辑本段
方向
施一公
施一公
施一公选择癌症作为自己的主攻方向,研究的课题是:细胞凋亡和癌症发生的分子机理。致癌原因一直是全球科学家致力研究的目标之一。2003年,由于破解了这一类生命科学之谜,当时年仅36岁的施一公获得全球生物蛋白研究学会颁发的“鄂文西格青年研究家奖”,成为这一奖项设立17年以来首位获奖的华裔学者。
迄今为止,施一公已在国际权威学术杂志发表学术论文100余篇,系统地揭示了哺乳动物、果蝇和线虫中细胞凋亡通路的分子机理,已有研究成果申请专利,用于治疗癌症的药物研发。
2010年,施一公获赛克勒国际生物物理学奖(赛克勒国际生物物理学奖(THE RAYMOND & BEVERLY SACKLER INTERNATIONAL PRIZE IN BIOPHYSICS)是由赛克勒夫妇捐赠设立,自2006年以来,每年奖励两到三位在国际生物物理学领域做出卓越成就、年龄在45岁以下的杰出科学家)。[5]
编辑本段
代表论文
(Representative Publications)
细胞凋亡
细胞凋亡领域
Programmed cell death (apoptosis):
1.Shiqian Qi, Yuxun Pang, Qi Hu, Qun Liu, Hua Li, Yulian Zhou, Tianxi He, Qionglin Liang, Yexing Liu, Xiaoqiu Yuan, Guoan Luo, Huilin Li, Jiawei Wang, Nieng Yan, and Yigong Shi (2010). Crystal structure of the Caenorhabditis elegans apoptosome reveals an octameric assembly of CED-4. Cell 141, 446-457.
2.Jong W. Yu, Philip D. Jeffrey, and Yigong Shi (2009). Mechanism of procaspase-8 activation by c-FLIPL. Proc Natl Acad Sci USA 106, 8169-8174. Epub 2009 May 4.
3.Nieng Yan, Jijie Chai, Eui Seung Lee, Lichuan Gu, Qun Liu, Jiaqing He, Jia-Wei Wu, David Kokel, Huilin Li, Quan Hao, Ding Xue, and Yigong Shi (2005). Structure of the CED-4/CED-9 complex provides insights into programmed cell death in Caenorhabditis elegans. Nature 437, 831–837.
4.Stefan J. Riedl, Wenyu Li, Yang Chao, Robert Schwarzenbacher, and Yigong Shi (2005). Structure of the apoptotic protease activating factor 1 (Apaf-1) bound to ADP. Nature 434, 926–933.
5.Nieng Yan, Lichuan Gu, David Kokel, Jijie Chai, Wenyu Li, Aidong Han, Lin Chen, Ding Xue, and Yigong Shi (2004). Structural, Biochemical and Functional Analyses of CED-9 Recognition by the Pro-apoptotic Proteins EGL-1 and CED-4. Mol. Cell 15, 999–1006.
6.Stefan J. Riedl and Yigong Shi (2004). Molecular mechanisms of caspase regulation during apoptosis. Nature Review – Mol. Cell. Biol. 5, 897–907.
7.Nieng Yan, Jia-Wei Wu, Jun R. Huh, Jijie Chai, Wenyu Li, Bruce A. Hay, and Yigong Shi (2004). Molecular mechanisms of DrICE inhibition by DIAP1 and removal of inhibition by Reaper, Hid, and Grim. Nature-Structural & Molecular Biology 11 (5), 420–428.
8.Yigong Shi (2004). Caspase Activation: Revisiting the Induced Proximity model. Cell 117, 855–858.
9.Jijie Chai, Nieng Yan, Jun R. Huh, Jia-Wei Wu, Wenyu Li, Bruce A. Hay, and Yigong Shi (2003). Molecular mechanism of Reaper/Grim/Hid-mediated suppression of DIAP1-dependent Dronc ubiquitination. Nature-Structural Biology 10, 892-898.
10.Eric N. Shiozaki, Jijie Chai, Daniel J. Rigotti, Stefan J. Riedl, Pingwei Li, Srinivasa M. Srinivasula, Emad S. Alnemri, Robert Fairman, and Yigong Shi (2003). Mechanism of XIAP-mediated Inhibition of Caspase-9. Mol. Cell 11, 519-527.
11.Yigong Shi (2002). Mechanisms of Caspase Activation and Inhibition During Apoptosis (commissioned review article). Mol Cell 9, 459-470.
12.Jijie Chai Qi Wu, Eric Shiozaki, Srinivasa M. Srinivasula, Emad S. Alnemri, and Yigong Shi (2001). Crystal Structure of a Caspase Zymogen: Mechanisms of Activation and Substrate Binding. Cell107, 399-407.
13.Jia-Wei Wu, Amy Cocina, Jijie Chai, Bruce Hay, and Yigong Shi (2001). Structural Analysis of a Functional DIAP1 Fragment Bound to Grim and Hid Peptides. Mol. Cell 8, 95-104.
14.Jijie Chai, Eric Shiozaki, Srinivasa M. Srinivasula, Qi Wu, Pinaki Datta, Emad S. Alnemri, and Yigong Shi (2001). Structural Basis of Caspase-7 Inhibition by XIAP. Cell 104, 769-780.
15.Stephen W. Fesik and Yigong Shi (2001). Controlling the Caspases. Science 294, 1477-1478.
16.Geng Wu, Jijie Chai, Tomeka Suber, Jia-Wei Wu, Chunying Du, Xiaodong Wang, and Yigong Shi (2000). Structural Basis of IAP Recognition by Smac/DIABLO. Nature408, 1008-1012.
17.Jijie Chai, Chunying Du, Jia-Wei Wu, Saw Kyin, Xiaodong Wang, and Yigong Shi (2000). Structural and Biochemical Basis of Apoptotic Activation by Smac/DIABLO. Nature 406, 855-862.
18.Hongxu Qin, Srinivasa M. Srinivasula, Geng Wu, Emad S. Alnemri, Yigong Shi (1999). Structural Basis of Procaspase-9 Recruitment by the Apoptotic Protease Activating Factor 1. Nature 399, 549-557.
膜蛋白
膜蛋白结构与功能领域Membrane protein structure and function:
1.Peng Zhang, Jiawei Wang, and Yigong Shi (2010). Structure and mechanism of the S component of a bacterial ECF transporter. Nature 468, 717-720. Epub 2010 Oct 24.
2.Xiang Gao, Lijun Zhou, Xuyao Jiao, Feiran Lu, Chuangye Yan, Xin Zeng, Jiawei Wang, and Yigong Shi (2010). Mechanism of substrate recognition and transport by an amino acid antiporter. Nature 463, 828-832. Epub 2010 Jan 20.
3.Yi Wang, Yongjian Huang, Jiawei Wang, Chao Cheng, Weijiao Huang, Peilong Lu, Ya-Nan Xu, Pengye Wang, Nieng Yan, and Yigong Shi (2009). Structure of the formate transporter FocA reveals a pentameric aquaporin-like channel. Nature 462, 467-472.
4.Xiang Gao, Feiran Lu, Lijun Zhou, Shangyu Dang, Linfeng Sun, Xiaochun Li, Jiawei Wang, and Yigong Shi (2009). Structure and Mechanism of an Amino Acid Antiporter. Science 324, 1565-1568. Epub 2009 May 28.
5.Xiaochun Li, Boyuan Wang, Lihui Feng, Hui Kang, Yang Qi, Jiawei Wang, and Yigong Shi (2009). Cleavage of RseA by RseP requires a carboxyl-terminal hydrophobic amino acid following DegS cleavage. Proc. Natl. Acad. Sci. USA 106, 14837-42 [Epub 2009 August 18].
6.Liang Feng, Hanchi Yan, Zhuoru Wu, Nieng Yan, Zhe Wang, Philip D. Jeffrey, and Yigong Shi (2007). Structure of a Site-2 Protease Family Intramembrane Metalloprotease. Science 318, 1608-1612.
7.Zhuoru Wu, Nieng Yan, Liang Feng, Adam Oberstein, Hanchi Yan, Rosanna P. Baker, Lichuan Gu, Philip D. Jeffrey, Sinisa Urban, and Yigong Shi (2006). Structural analysis of a rhomboid family intramembrane protease reveals a gating mechanism for substrate entry. Nature Structural & Molecular Biology 13, 1084-1091. 2006 Nov 10; [Epub ahead of print].
去磷酸化酶
蛋白去磷化酶领域
Protein phosphatase 2A (PP2A):
1.Yigong Shi (2009). Structure and Mechanism of Protein Serine/Threonine Phosphatases. Cell 139, 468-484.
2.Yongna Xing, Zhu Li, Yu Chen, Philip D. Jeffery, and Yigong Shi (200

. Structural Mechanism of Demethylation and Inaction of Protein Phosphatase 2A. Cell 133, 154-163.
3. Yu Chen, Yanhui Xu, Qing Bao, Yongna Xing, Zhu Li, Zheng Lin, Jeffry Stock, Philip P. Jeffrey, Yigong Shi (2007) Structural and biochemical insights into the regulation of protein phosphatase 2A by small t antigen of SV40. Nature Struct Mol Biol. 14(6), 527-34. Epub 2007 May 27.
4.Yanhui Xu, Xing Yongna, Yu Chen, Yang Chao, Zheng Lin, Eugene Fan, Jong W. Yu, Stefan Strack, Philip D. Jeffrey, and Yigong Shi (2006). Structure of the Protein Phosphatase 2A Holoenzyme. Cell 127, 1239–1251.
5.Xing Yongna, Yanhui Xu, Yu Chen, Philip D. Jeffrey, Yang Chao, Zheng Lin, Zhu Li, Stefan Strack, Jeffry B Stock, and Yigong Shi (2006). Structure of Protein Phosphatase 2A Bound to Tumor-inducing Toxins. Cell 127, 341-352.
6.Yang Chao, Yongna Xing, Yu Chen, Yanhui Xu, Zheng Lin, Zhu Li, Philip D. Jeffrey, Jeffry B. Stock and Yigong Shi (2006). Structure and Mechanism of the Phosphotyrosyl Phosphatase Activator. Mol. Cell 23, 535-546.
质量控制
蛋白降解与质量控制领域Protein degradation and quality control:
1.Feng Wang, Ziqing Mei, Yutao Qi, Chuangye Yan, Siheng Xiang, Qi Hu, Jiawei Wang, and Yigong Shi. (2010) Structure and mechanism of the hexameric MecA-ClpC molecular machine. Nature,2011 Mar 2. [Epub ahead of print].
2.Fan Zhang , Zhuoru Wu, Ping Zhang, Geng Tian, Daniel Finley, and Yigong Shi (2009). Mechanism of substrate unfolding and translocation by the regulatory particle of the proteasome from Methanocaldococcus jannaschii. Mol Cell 34, 485-496.
3.Fan Zhang , Min Hu, Geng Tian, Ping Zhang, Daniel Finley, Philip D. Jeffrey, and Yigong Shi (2009). Structural insights into the regulatory particle of the proteasome from Methanocaldococcus jannaschii. Mol Cell 34, 473-484.
4.Nieng Yan and Yigong Shi (2007). Allosteric Activation of a Bacterial Stress Sensor. Cell 131, 441-443.
5.Min Hu, Lichuan Gu, Muyang Li, Philip D. Jeffrey, Wei Gu, and Yigong Shi (2006). Structural Basis of Competitive Recognition of p53 and MDM2 by HAUSP/USP7: Implications for the Regulation of the p53/MDM2 Pathway. PloS Biology 4, e27.
6.Min Hu, Pingwei Li, Ling Song, Philip D. Jeffrey, Tatiana A. Chenova, Keith D. Wilkinson, Robert E. Cohen, and Yigong Shi (2005). Structure and mechanisms of the proteasome-associated deubiquitinating enzyme USP14. EMBO J. 24, 3747-3756. Epub 2005 Oct. 6.
7.Min Hu, Pingwei Li, Muyang Li, Wenyu Li, Tingting Yao, Jia-Wei Wu, Wei Gu, Robert E. Cohen, and Yigong Shi (2002). Crystal Structure of a UBP-family Deubiquitinating Enzyme in Isolation and in Complex with Ubiquitin Aldehyde. Cell 111, 1041-1054.
信号转导
SMAD蛋白信号转导领域
SMAD proteins in TGF-b signaling:
1.Yigong Shi and Joan Massagué (2003). Mechanisms of TGF-b signaling from Cell Membrane to the Nucleus. (commissioned review article) Cell 113, 685-700.
2.Jia-Wei Wu, Ariel R. Krawitz, Jijie Chai, Wenyu Li, Fangjiu Zhang, Kunxin Luo, and Yigong Shi (2002). Structural Mechanism of Smad4 Recognition by the Nuclear Oncoprotein Ski: Insight on Ski-Mediated Repression of TGF-b Signaling. Cell 111, 357-367.
3.Jia-Wei Wu, Min Hu, Jijie Chai, Morgan Huse, Carey Li, Saw Kyin, Robert Fairman, Tom Muir, Joan Massagué, and Yigong Shi (2001). Crystal Structure of a Phosphorylated Smad2: Recognition of Phosphoserine Motif and Insights on Smad Function in TGF-b Signaling. Mol. Cell 8, 1277-1289.
4.Geng Wu, Ye-Guang Chen, Barish Ozdamar, Cassie Gyuricza, P. Andrew Chong, Jeffrey L. Wrana, Joan Massagué, and Yigong Shi (2000). Structural Basis of Smad2 Recruitment by the Smad Anchor for Receptor Activation (SARA). Science 287, 92-97.
5.Yigong Shi, Yan-Fei Wang, Lata Jayaraman, Haijuan Yang, Joan Massagué, and Nikola Pavletich (199

. Crystal Structure of A Smad MH1 Domain Bound to DNA: Insights on DNA-binding in TGF-b Signaling. Cell, 94, 585-594.
6.Yigong Shi, Akiko Hata, Joan Massagué and Nikola P. Pavletich (1997) A structural basis for mutational inactivation of the tumour suppressor Smad4. Nature 388, 87-93.
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