公海彩船: 课题组长
姓名:
徐菲教授 研究员 博士生导师, PhD, 教授
职务:
所在院所:
公海彩船、iHuman研究所
荣誉称号:
教育经历:
-
2002/09—2006/07,中国科学技术大学,学士
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2006/07—2011/06,美国斯克里普斯研究所,博士
博士后及工作经历:
- 2011/08—2013/09,美国锐意生物医药有限公司,研发顾问
- 2013/09—2014/08,上海科技大学,iHuman研究所,副研究员
- 2014/08—2019/12,上海科技大学,公海彩船、iHuman研究所,助理教授(TENURE-TRACK)
- 2019/12—公海彩船/11,上海科技大学,公海彩船、iHuman研究所,副教授(TENURED)
- 公海彩船/11—至今,上海科技大学,公海彩船、iHuman研究所,教授(TENURED)
公海彩船: 课题组简介
研究内容:
我们的研究方向专注于使用世界领先的膜蛋白结构生物学和细胞生物学相结合的方法,并通过广泛的跨技术领域合作,深入研究一类与人类疾病密切相关、但其结构和机制尚不清楚的信号转导受体--GPCR靶点。这些靶点主要包括内源性配体未知的一类GPCR--孤儿受体、调节Wnt信号通路的一类非典型GPCR--卷曲受体,以及与精神调控密切相关的受体和离子通道等。我们的研究涵盖靶点蛋白的三维结构和多聚形式、配体识别与调控机制、受体激活或自激活机制、信号转导复合物结构与功能等多个方面。通过深入了解这些蛋白的结构和功能,为药物小分子和抗体的筛选提供指导,推动相关药物的发现与研发。
课题组网站:
http://xulab.shanghaitech.edu.cn
公海彩船: 研究成果展示
课题组使用最前沿的GPCR 相关技术解决重要的生物学问题及发展药物开发与应用。报道了冰毒等成瘾药物靶点TAAR1受体的结构,阐释了这一精神疾病重要靶标的配体识别与结构药理学机制,论文发表在公海彩船年11月的《Nature》上;解析了首个人源孤儿受体GPR52不同功能状态的三维结构,提出了具有高本底活性的孤儿受体特有的自激活机制,相关论文及一系列后续工作发表在2020年2月的《Nature》、公海彩船年的《Nature Communications》和《Cell Discovery》等期刊上;卷曲受体家族首个蛋白结构的解析揭示了该家族蛋白的独特结构特征和作为潜在癌症靶点的研究潜力,相关论文及后续工作发表在2018 年7 月的《Nature》、2021年的《Cell Research》、以及最新的《Cell Discovery》上;解析了心血管疾病靶标人源apelin 受体结合类天然多肽配体的高分辨率结构,破解了A类GPCR二聚化的谜题,相关工作发表在2022年的《Nature Structural & Molecular Biology》以及2017 年的《Structure》上。此外,围绕精神疾病、肿瘤等GPCR和离子通道靶标,做出了一系列原创科学发现,相关成果发表在《Neuron》、《Protein & Cell》、《J Med Chem》等学术期刊上。
公海彩船: 代表性论文(*第一作者,#通讯作者)
- 1. Heng Liu*, You Zheng*, Yue Wang*, Yumeng Wang*, Xinheng He, Peiyu Xu, Sijie Huang, Qingning Yuan, Xinyue Zhang, Ling Wang, Kexin Jiang, Hong Chen, Zhen Li, Wenbin Liu##, Sheng Wang##, H. Eric Xu##, Fei Xu##.Recognition of methamphetamine and other amines by trace amine receptor TAAR1.Nature. Nov 公海彩船.
- 2. Li, Cuixia*; Wu, Yiran; Wang, Wenli; Xu, Lu; Zhou, Yan; Yue, Yang; Wu, Tingting; Yang, Meifang; Qiu, Yanli; Huang, Minhao; Zhou, Fangfang; Zhou, Yiqing; Hao, Piliang; Lin, Zhixiong; Wang, Ming-Wei; Zhao, Suwen#; Yang, Dehua#; Xu, Fei#; Tao, Houchao#; .Structure-Based Ligand Discovery Targeting the Transmembrane Domain of Frizzled Receptor FZD7.JOURNAL OF MEDICINAL CHEMISTRY. 05 Sep 公海彩船.
- 3. Lin, Xi*; Jiang, Shan*; Wu, Yiran; Wei, Xiaohu; Han, Gye-Won; Wu, Lijie; Liu, Junlin; Chen, Bo; Zhang, Zhibin; Zhao, Suwen; Cherezov, Vadim; Xu, Fei#.The activation mechanism and antibody binding mode for orphan GPR20.CELL DISCOVERY;. 01 Dec 公海彩船. 9(1).
- 4. Lin Xi*, Chen B*, Wu Y*, Han Y, Qi A, Wang J, Yang Z, Wei X, Zhao T, Wu L, Xie X, Sun J, Zheng J#, Zhao S#, Xu F#.Cryo-EM structures of orphan GPR21 signaling complexes.Nature Communications. Jan 公海彩船.
- 5. Yue, Yang*; Liu, Lier*; Wu, Li-Jie*; Wu, Yiran; Wang, Ling; Li, Fei; Liu, Junlin; Han, Gye-Won; Chen, Bo; Lin, Xi; Brouillette, Rebecca L.; Breault, Emile; Longpre, Jean-Michel; Shi, Songting; Lei, Hui; Sarret, Philippe; Stevens, Raymond C.; Hanson, Michael A.; Xu, Fei#.Structural insight into apelin receptor-G protein stoichiometry.NATURE STRUCTURAL & MOLECULAR BIOLOGY. Jul 2022. 29(7).
- 6. Chen Yuxiang*, Chen B*, Wu T*, Zhou F, Xu F#.Cryo-EM structure of human κ-opioid receptor-Gi complex bound to an endogenous agonist dynorphin A.Protein & Cell. Aug 2022.
- 7. Zheng, You*; Liu, Heng; Chen, Yuxin; Dong, Shaowei; Wang, Fang; Wang, Shengyi; Li, Geng-Lin; Shu, Yilai#; Xu, Fei#.Structural insights into the lipid and ligand regulation of a human neuronal KCNQ channel.NEURON. 19 Jan 2022. 110(2).
- 8. Xu, Lu*; Chen, Bo; Schihada, Hannes; Wright, Shane C.; Turku, Ainoleena; Wu, Yiran; Han, Gye-Won; Kowalski-Jahn, Maria; Kozielewicz, Pawel; Bowin, Carl-Fredrik; Zhang, Xianjun; Li, Chao; Bouvier, Michel; Schulte, Gunnar#; Xu, Fei#.Cryo-EM structure of constitutively active human Frizzled 7 in complex with heterotrimeric G(s).CELL RESEARCH. Dec 2021.
- 9. Lin, Xi*; Li, Mingyue*; Wang, Niandong*; Wu, Yiran*; Luo, Zhipu; Guo, Shimeng; Han, Gye-Won; Li, Shaobai; Yue, Yang; Wei, Xiaohu; Xie, Xin; Chen, Yong; Zhao, Suwen; Wu, Jian#; Lei, Ming#; Xu, Fei#.Structural basis of ligand recognition and self-activation of orphan GPR52.NATURE. 19 Feb 2020.
- 10. Yang, Shifan*; Wu, Yiran; Xu, Ting-Hai; de Waal, Parker W.; He, Yuanzheng; Pu, Mengchen; Chen, Yuxiang; DeBruine, Zachary J.; Zhang, Bingjie; Zaidi, Saheem A.; Popov, Petr; Guo, Yu; Han, Gye Won; Lu, Yang; Suino-Powell, Kelly; Dong, Shaowei; Harikumar, Kaleeckal G.; Miller, Laurence J.; Katritch, Vsevolod; Xu, H. Eric; Shui, Wenqing; Stevens, Raymond C.; Melcher, Karsten; Zhao, Suwen; Xu, Fei#.Crystal structure of the Frizzled 4 receptor in a ligand-free state.NATURE. 2018. 560(7720):666-670.
- 11. Zhang, Xianjun*; Zhao, Fei; Wu, Yiran; Yang, Jun; Han, Gye Won; Zhao, Suwen; Ishchenko, Andrii; Ye, Lintao; Lin, Xi; Ding, Kang; Dharmarajan, Venkatasubramanian; Griffin, Patrick R.; Gati, Cornelius; Nelson, Garrett; Hunter, Mark S.; Hanson, Michael A.; Cherezov, Vadim; Stevens, Raymond C.; Tan, Wenfu#; Tao, Houchao#; Xu, Fei#.Crystal structure of a multi-domain human smoothened receptor in complex with a super stabilizing ligand.NATURE COMMUNICATIONS. 17 May 2017. 8(1).
- 12. Zhang, Xianjun*; Dong, Shaowei; Xu, Fei#.Structural and Druggability Landscape of Frizzled G Protein-Coupled Receptors.TRENDS IN BIOCHEMICAL SCIENCES. Dec 2018. 43(12):1033-1046.
- 13. Xu, Fei*; Wu, Huixian; Katritch, Vsevolod; Han, Gye Won; Jacobson, Kenneth A.; Gao, Zhan-Guo; Cherezov, Vadim; Stevens, Raymond C.#.Structure of an Agonist-Bound Human A(2A) Adenosine Receptor.SCIENCE. 2011. 332(6027):322-327.
- 14. Zhang, Xianjun*; Stevens, Raymond C.; Xu, Fei#.The importance of ligands for G protein-coupled receptor stability.TRENDS IN BIOCHEMICAL SCIENCES. Feb 2015. 40(2):79-87.
- 15. Ma, Yingli*; Yue, Yang; Ma, Yanbin; Zhang, Qing; Zhou, Qingtong; Song, Yunpeng; Shen, Yuqing; Li, Xun; Ma, Xiaochuan; Li, Chao; Hanson, Michael A.; Han, Gye Won; Sickmier, E. Allen; Swaminath, Gayathri; Zhao, Suwen; Stevens, Raymond C.; Hu, Liaoyuan A.; Zhong, Wenge; Zhang, Mingqiang; Xu, Fei#.Structural Basis for Apelin Control of the Human Apelin Receptor.STRUCTURE. 06 Jun 2017. 25(6):858-+.
- 16. Xu, Fei*; Liu, Wei; Hanson, Michael A.; Stevens, Raymond C.; Cherezov, Vadim#.Development of an Automated High Throughput LCP-FRAP Assay to Guide Membrane Protein Crystallization in Lipid Mesophases.CRYSTAL GROWTH & DESIGN. 2011. 11(4):1193-1201.
- 17. Xu, Fei*; Stevens, Raymond C.#.Trapping Small Caffeine in a Large GPCR Pocket.STRUCTURE. 2011. 19(9):1204-1207.
- 18. Liu, Wei*; Chun, Eugene; Thompson, Aaron A.; Chubukov, Pavel; Xu, Fei; Katritch, Vsevolod; Han, Gye Won; Roth, Christopher B.; Heitman, Laura H.; IJzerman, Adriaan P.; Cherezov, Vadim#; Stevens, Raymond C.#.Structural Basis for Allosteric Regulation of GPCRs by Sodium Ions.SCIENCE. 2012. 337(6091):232-236.
- 19. Chun, Eugene*; Thompson, Aaron A.; Liu, Wei; Roth, Christopher B.; Griffith, Mark T.; Katritch, Vsevolod; Kunken, Joshua; Xu, Fei; Cherezov, Vadim; Hanson, Michael A.#; Stevens, Raymond C.#.Fusion Partner Toolchest for the Stabilization and Crystallization of G Protein-Coupled Receptors.STRUCTURE. 2012. 20(6):967-976.
- 20. Tosh, Dilip K.*; Phan, Khai; Gao, Zhan-Guo; Gakh, Andrei A.; Xu, Fei; Deflorian, Francesca; Abagyan, Ruben; Stevens, Raymond C.; Jacobson, Kenneth A.#; Katritch, Vsevolod#.Optimization of Adenosine 5 '-Carboxamide Derivatives as Adenosine Receptor Agonists Using Structure-Based Ligand Design and Fragment Screening.JOURNAL OF MEDICINAL CHEMISTRY. 2012. 55(9):4297-4308.
- 21. Deflorian, Francesca*; Kumar, T. Santhosh; Phan, Khai; Gao, Zhan-Guo; Xu, Fei; Wu, Huixian; Katritch, Vsevolod; Stevens, Raymond C.; Jacobson, Kenneth A.#.Evaluation of Molecular Modeling of Agonist Binding in Light of the Crystallographic Structure of an Agonist-Bound A(2A) Adenosine Receptor.JOURNAL OF MEDICINAL CHEMISTRY. 2012. 55(1):538-552.
- 22. Xue, Dongxiang*; Ye, Lintao; Zheng, Jun; Wu, Yiran; Zhang, Xianjun; Xu, Yueming; Li, Tao; Stevens, Raymond C.; Xu, Fei; Zhuang, Min; Zhao, Suwen; Zhao, Fei#; Tao, Houchao#.The structure-based traceless specific fluorescence labeling of the smoothened receptor.ORGANIC & BIOMOLECULAR CHEMISTRY. 07 Jul 2019. 17(25):6136-6142.
- 23. Ye, Lintao*; Ding, Kang; Zhao, Fei; Liu, Xiaoyan; Wu, Yiran; Liu, Yang; Xue, Dongxiang; Zhou, Fang; Zhang, Xianjun; Stevens, Raymond C.; Xu, Fei; Zhao, Suwen#; Tao, Houchao#.A structurally guided dissection-then-evolution strategy for ligand optimization of smoothened receptor.MEDCHEMCOMM. Jun 2017. 8(6):1332-1336.
- 24. Zhao, Huan*; Tian, Xueying; He, Lingjuan; Li, Yan; Pu, Wenjuan; Liu, Qiaozhen; Tang, Juan; Wu, Jiaying; Cheng, Xin; Liu, Yang; Zhou, Qingtong; Tan, Zhen; Bai, Fan; Xu, Fei; Smart, Nicola; Zhou, Bin#.Apj(+) Vessels Drive Tumor Growth and Represent a Tractable Therapeutic Target.CELL REPORTS. 30 Oct 2018. 25(5):1241-+.
- 25. Zhou, F.*; Ding, K.; Zhou, Y.; Liu, Y.; Liu, X.; Zhao, F.; Wu, Y.; Zhang, X.; Xu, F.; Zhao, S.; Tao, H..Determination of an underneath binding in the transmembrane domain of smoothened receptor.JOURNAL OF BIOENERGETICS AND BIOMEMBRANES. Dec 2018. 50(6):510-510.
- 26. Lin, X.*; Xu, F..Toward the first orphan GPCR structure.JOURNAL OF BIOENERGETICS AND BIOMEMBRANES. Dec 2018. 50(6):559-559.
- 27. Zhou, Fang*; Ding, Kang; Zhou, Yiqing; Liu, Yang; Liu, Xiaoyan; Zhao, Fei; Wu, Yiran; Zhang, Xianjun; Tan, Qiwen; Xu, Fei; Tan, Wenfu; Xiao, Youli#; Zhao, Suwen#; Tao, Houchao#.Colocalization Strategy Unveils an Underside Binding Site in the Transmembrane Domain of Smoothened Receptor.JOURNAL OF MEDICINAL CHEMISTRY. 14 Nov 2019. 62(21):9983-9989.
- 28. Lin, Xi*; Chen, Bo; Wu, Yiran; Han, Yingqi; Qi, Ao; Wang, Junyan; Yang, Zhao; Wei, Xiaohu; Zhao, Tingting; Wu, Lijie; Xie, Xin; Sun, Jinpeng; Zheng, Jie#; Zhao, Suwen#; Xu, Fei#.Cryo-EM structures of orphan GPR21 signaling complexes.NATURE COMMUNICATIONS;. 01 Dec 公海彩船. 14(1).
公海彩船: 奖励
- 1. 2014年,上海市浦江人才
- 2. 2018年,海外高层次人才(青千)
- 3. 2019年,上海市优秀学术带头人
- 4. 2020年,药明康德生命化学研究奖
- 5. 2021年,上海市教育系统三八红旗手
- 6. 2022年,上海市东方英才计划领军项目
公海彩船: 课题组成员及合影
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姓名:岳洋
身份:高级工程师
在组时间:2014/07-至今
邮箱:yueyang@@shanghaitech.edu.cn
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姓名:林浠
身份:副研究员
在组时间:2020/8-至今
邮箱:linxi@@shanghaitech.edu.cn
-
姓名:徐鹭
身份:博士后
在组时间:2022/1-至今
邮箱:xulu@@shanghaitech.edu.cn
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姓名:刘立尔
身份:博士研究生
在组时间:2017/01-至今
邮箱:liule@@shanghaitech.edu.cn
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姓名:张智斌
身份:博士研究生
在组时间:2019/09-至今
邮箱:zhangzhb@shanghaitech.edu.cn
-
姓名:姜可新
身份:博士研究生
在组时间:2019/09-至今
邮箱:jiangkx1@shanghaitech.edu.cn
-
姓名:李翠霞
身份:博士研究生
在组时间:2019/09-至今
邮箱:licx@shanghaitech.edu.cn
-
姓名:蒋姗
身份:博士研究生
在组时间:2020/9-至今
邮箱:jiangshan1@shanghaitech.edu.cn
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姓名:张忠原
身份:博士研究生
在组时间:2021/9-至今
邮箱:zhangzhy5@shanghaitech.edu.cn
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姓名:严鹏飞
身份:硕士研究生
在组时间:2021/9-至今
邮箱:yanpf@shanghaitech.edu.cn
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姓名:许紫依
身份:硕士研究生
在组时间:2022/09-至今
邮箱:xuzy12022@shanghaitech.edu.cn
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姓名:娜曼
身份:硕士研究生
在组时间:2022/09-至今
邮箱:naman2022@shanghaitech.edu.cn
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姓名:徐可馨
身份:硕士研究生
在组时间:2022/09-至今
邮箱:xukx2022@shanghaitech.edu.cn
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姓名:赵敏萱
身份:本科生
在组时间:公海彩船/04-至今
邮箱:zhaomx1@shanghaitech.edu.cn
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