Principal investigator
Name:
Wenqing XuProfessor , PhD, Professor
Position:
Affiliation:
School of Life Science and Technology
Honor:
Education Background:
- 1980-1985, University of Science and Technology of China (USTC), B.S.
- 1991-1995, Massachusetts Institute of Technology (MIT), Ph.D.
Working Experience:
- 1995-1999, Harvard Medical School, Postdoctoral Fellow
- 1999-2003, University of Washington School of Medicine (in Seattle), Assistant Professor (TENURE-TRACK)
- 2004-2008, University of Washington School of Medicine (in Seattle), Associate Professor (TENURED)
- 2009-2019, University of Washington School of Medicine (in Seattle), Full Professor (TENURED)
- 2019/08-Present, ShanghaiTech University, School of Life Science and Technology, Full Professor (TENURED)
Group Introduction
Research Area:
Structural and Mechanistic Studies of Cell Signaling and Protein Design
Research Interests:
In all life forms, cells must be able to perceive and correctly respond to their environment. In humans, dysregulation of cell signaling pathways can lead to many diseases including cancers. We aim to understand how cells sense their environment and transduce signals in cells under normal and pathologic conditions, using a combination of structural (X-ray crystallographic and cryo-EM) and biochemical studies. In particular, we are interested in the Wnt signaling pathway, which plays critical roles in embryonic development, stem cell homeostasis and tissue regeneration. Our work helps to lay the foundation for developing novel therapeutic approaches for disease treatment.
Representative Publications (*First Author, # Corresponding Author)
- 1. Gangyu Sun*, Xiang Li*, Jiaojiao Hu, Tianbin Yang, Cong Liu, Zhizhi Wang, Dan Li, Wenqing Xu .De novo design of protein binders to stabilize monomeric TDP-43 and inhibit its pathological aggregation.PNAS. Sep 2025.
- 2. Jinxin Wang*, Qingjing He*, Yuqiang Zeng*, Youming Wu*, Mufeng Wang, Wenqing Xu, Zhizhi Wang, Xiaohui Zhang.A series of precise and controllable base editors with split-TadA-8e.Molecular Therapy Nucleic Acids. Sep 2025.
- 3. Hongyang Wang*, Ying Zheng, Tiantian Wang, Xue Zhang, Peipei Wang, Chuancun Wei, Hongyue Li, Quan Wang, Lu Zhang, Xisong Ke, Wenqing Xu.Structure-based engineering of the midnolin-proteasome pathway for targeted protein degradation.Protein & Cell. Aug 2025.
- 4. Shuyi Zeng*, Xingyu Xiong, Houfang Long, Qianhui Xu, Yifan Yu, Bo Sun, Cong Liu, Zhizhi Wang, Wenqing Xu, Shengnan Zhang & Dan Li.Design of Ig-like binders targeting α-synuclein fibril for mitigating its pathological activities.Nature Communications. Aug 2025.
- 5. Zhao, Yue*; Wang, Hongyang; Wu, Ping; Zhang, Yanan; Wang, Zhizhi; Xu, Wenqing.Development of nanobody-based PROTAC (NbTAC) for ROR1 degradation by RNF149.INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES. 01 Jul 2025. 319.
- 6. Dai, Zhizhuo*; Yang, Tianbin; Xu, Wenqing; Wang, Zhizhi.Development of a chemically induced dissociation system via phage surface-displayed nanobody screening.FEBS LETTERS. 31 May 2025.
- 7. Shengxi Shen*; Ping Wang; Pei Wu; Pengyu Huang; Tian Chi; Wenqing Xu; Ying Xi.CasRx-based Wnt activation promotes alveolar regeneration while ameliorating pulmonary fibrosis in a mouse model of lung injury.MOLECULAR THERAPY. 06 Nov 2024. 32(11):3974-3989.
- 8. wwPDB Consortium*: Jack Turner, Sanja Abbott, Neli Fonseca, Ryan Pye, Lucas Carrijo, Amudha Kumari Duraisamy, Osman Salih, Zhe Wang, Gerard J Kleywegt, Kyle L Morris, Ardan Patwardhan, Stephen K Burley, Gregg Crichlow, Zukang Feng, Justin W Flatt, Sutapa Ghosh, Brian P Hudson, Catherine L Lawson, Yuhe Liang, Ezra Peisach, Irina Persikova, Monica Sekharan, Chenghua Shao, Jasmine Young, Sameer Velankar, David Armstrong, Marcus Bage, Wesley Morellato Bueno, Genevieve Evans, Romana Gaborova, Sudakshina Ganguly, Deepti Gupta, Deborah Harrus, Ahsan Tanweer, Manju Bansal, Vetriselvi Rangannan, Genji Kurisu, Hasumi Cho, Yasuyo Ikegawa, Yumiko Kengaku, Ju Yaen Kim, Satomi Niwa, Junko Sato, Ayako Takuwa, Jian Yu, Jeffrey C Hoch, Kumaran Baskaran, Wenqing Xu, Weizhe Zhang, Xiaodan Ma.EMDB-the Electron Microscopy Data Bank.Nucleic Acids Research. Jan 2024.
- 9. Yao, Hebang*; Wang, Hongyang*; Zhang, Zhaoyong*; Lu, Yuchi*; Zhang, Zhiying; Zhang, Yu; Xiong, Xinyi; Wang, Yanqun; Wang, Zhizhi; Yang, Haitao; Zhao, Jincun; Xu, Wenqing.A potent and broad-spectrum neutralizing nanobody for SARS-CoV-2 viruses, including all major Omicron strains.MEDCOMM. 26 Oct 2023.
- 10. Wang, Hongyang*; Bienz, Mariann; Yan, Xiao-Xue; Xu, Wenqing.Structural basis of the interaction between BCL9-Pygo and LDB-SSBP complexes in assembling the Wnt enhanceosome.NATURE COMMUNICATIONS. 22 Jun 2023. 14(1).
- 11. Xu, Wenqing*; Velankar, Sameer; Patwardhan, Ardan; Hoch, Jeffrey C.; Burley, Stephen K.; Kurisu, Genji.Announcing the launch of Protein Data Bank China as an Associate Member of the Worldwide Protein Data Bank Partnership.ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY. 01 Sep 2023. 79.
- 12. Tian, Li-Fei*; Gao, Hongwei; Yang, Shuyu; Liu, Yan-Ping; Li, Mingzhou; Xu, Wenqing; Yan, Xiao-Xue.Structure and function of extreme TLS DNA polymerase TTEDbh from Thermoanaerobacter tengcongensis.INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES. 31 Dec 2023. 253.
- 13. Pavic, Karolina*; Gupta, Nikhil; Omella, Judit Domenech; Derua, Rita; Aakula, Anna; Huhtaniemi, Riikka; Maatta, Juha A.; Hofflin, Nico; Okkeri, Juha; Wang, Zhizhi; Kauko, Otto; Varjus, Roosa; Honkanen, Henrik; Abankwa, Daniel; Kohn, Maja; Hytonen, Vesa P.; Xu, Wenqing; Nilsson, Jakob; Page, Rebecca; Janssens, Veerle; Leitner, Alexander; Westermarck, Jukka.Structural mechanism for inhibition of PP2A-B56α and oncogenicity by CIP2A.NATURE COMMUNICATIONS;. 01 Dec 2023. 14(1).
- 14. Tian, Li-Fei*; Kuang, Xiaolin; Ding, Ke; Gao, Hongwei; Tang, Qun; Yan, Xiao-Xue; Xu, Wenqing.Biochemical and Structural Analyses Shed Light on the Mechanisms of RadD DNA Binding and Its ATPase from Escherichia coli.INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. 2023. 24(1).
- 15. Chen, Lianqi*; Liu, Yan-Ping; Tian, Li-Fei; Li, Mingzhou; Yang, Shuyu; Wang, Song; Xu, Wenqing; Yan, Xiao-Xue.Structural Basis of the Interaction between Human Axin2 and SIAH1 in the Wnt/beta-Catenin Signaling Pathway.BIOMOLECULES. 01 Apr 2023. 13(4).
- 16. Liu, Huisi*; Wu, Weiwei*; Sun, Gangyu*; Chia, Tiongsun*; Cao, Lei; Liu, Xiaodan; Guan, Jian; Fu, Fenggen; Yao, Ying; Wu, Zhihai; Zhou, Shuaixiang; Wang, Jie; Lu, Jia; Kuang, Zhihui; Wu, Min; He, Luan; Shao, Zhiyuan; Wu, Dongdong; Chen, Bingliang; Xu, Wenqing; Wang, Zhizhi; He, Kaijie.Optimal target saturation of ligand-blocking anti-GITR antibody IBI37G5 dictates FcγR-independent GITR agonism and antitumor activity.CELL REPORTS MEDICINE. 21 Jun 2022. 3(6).
- 17. Jia, Lina*; Liu, Yan-Ping; Tian, Li-Fei; Xiong, Chao; Xu, Xin; Qu, Honge; Xiong, Weixi; Zhou, Dong; Wang, Feng; Liu, Zheng; Yan, Xiao-Xue; Xu, Wenqing; Tang, Lin.Potent neutralizing RBD-specific antibody cocktail against SARS-CoV-2 and its mutant.MEDCOMM. Sep 2021. 2(3):442-452.
- 18. Zhong, Qing*; Zhao, Yanyu; Ye, Fangfei; Xiao, Zaiyu; Huang, Gaoxingyu; Xu, Meng; Zhang, Yuanyuan; Zhan, Xiechao; Sun, Ke; Wang, Zhizhi; Cheng, Shanshan; Feng, Shan; Zhao, Xiuxiu; Zhang, Jizhong; Lu, Peilong; Xu, Wenqing; Zhou, Qiang; Ma, Dan.Cryo-EM structure of human Wntless in complex with Wnt3a.NATURE COMMUNICATIONS. 27 Jul 2021. 12(1).
- 19. Zhao, Yao*; Du, Xiaoyu*; Duan, Yinkai*; Pan, Xiaoyan*; Sun, Yifang*; You, Tian*; Han, Lin*; Jin, Zhenming; Shang, Weijuan; Yu, Jing; Guo, Hangtian; Liu, Qianying; Wu, Yan; Peng, Chao; Wang, Jun; Zhu, Chenghao; Yang, Xiuna; Yang, Kailin; Lei, Ying; Guddat, Luke W.; Xu, Wenqing; Xiao, Gengfu; Sun, Lei; Zhang, Leike; Rao, Zihe; Yang, Haitao.High-throughput screening identifies established drugs as SARS-CoV-2 PLpro inhibitors.PROTEIN & CELL. Nov 2021. 12(11):877-888.
- 20. Sun, Gangyu*; Xue, Lulu*; He, Qingjing; Zhao, Yue; Xu, Wenqing; Wang, Zhizhi.Structural insights into SARS-CoV-2 infection and therapeutics development.STEM CELL RESEARCH. Apr 2021. 52.
- 21. Liu, Fengjiang*; Liang, Jingxi*; Zhang, Bing*; Gao, Yan*; Yang, Xiuna; Hu, Tianyu; Yang, Haitao; Xu, Wenqing; Guddat, Luke W.; Rao, Zihe.Structural basis of trehalose recycling by the ABC transporter LpqY-SugABC.SCIENCE ADVANCES. Oct 2020. 6(44):eabb9833.
- 22. Wang, Quan*; Wu, Jiqin*; Wang, Haofeng*; Gao, Yan*; Liu, Qiaojie*; Mu, An; Ji, Wenxin; Yan, Liming; Zhu, Yan; Zhu, Chen; Fang, Xiang; Yang, Xiaobao; Huang, Yucen; Gao, Hailong; Liu, Fengjiang; Ge, Ji; Sun, Qianqian; Yang, Xiuna; Xu, Wenqing; Liu, Zhijie; Yang, Haitao; Lou, Zhiyong; Jiang, Biao; Guddat, Luke W.; Gong, Peng; Rao, Zihe.Structural Basis for RNA Replication by the SARS-CoV-2 Polymerase.CELL. 23 Jul 2020. 182(2):417.
- 23. 许文青*; 丛尧; 王权.冷冻电镜:新时代蛋白质科学和药物研发的利器.张江科技评论;. 28 Jun 2020. 3:43-45.
- 24. Zhang, Lu*; Zhao, Yao*; Gao, Yan; Wu, Lijie; Gao, Ruogu; Zhang, Qi; Wang, Yinan; Wu, Chengyao; Wu, Fangyu; Gurcha, Sudagar S.; Veerapen, Natacha; Batt, Sarah M.; Zhao, Wei; Qin, Ling; Yang, Xiuna; Wang, Manfu; Zhu, Yan; Zhang, Bing; Bi, Lijun; Zhang, Xian'en; Yang, Haitao; Guddat, Luke W.; Xu, Wenqing; Wang, Quan; Li, Jun; Besra, Gurdyal S.; Rao, Zihe.Structures of cell wall arabinosyltransferases with the anti-tuberculosis drug ethambutol.SCIENCE. 12 Jun 2020. 368(6496):1211.
- 25. Gao, Yan*; Yan, Liming*; Huang, Yucen*; Liu, Fengjiang*; Zhao, Yao; Cao, Lin; Wang, Tao; Sun, Qianqian; Ming, Zhenhua; Zhang, Lianqi; Ge, Ji; Zheng, Litao; Zhang, Ying; Wang, Haofeng; Zhu, Yan; Zhu, Chen; Hu, Tianyu; Hua, Tian; Zhang, Bing; Yang, Xiuna; Li, Jun; Yang, Haitao; Liu, Zhijie; Xu, Wenqing; Guddat, Luke W.; Wang, Quan; Lou, Zhiyong; Rao, Zihe.Structure of the RNA-dependent RNA polymerase from COVID-19 virus.SCIENCE. 15 May 2020. 368(6492):779-+.
- 26. Zhang, Lu*; Zhao, Yao*; Gao, Ruogu*; Li, Jun; Yang, Xiuna; Gao, Yan; Zhao, Wei; Gurcha, Sudagar S.; Veerapen, Natacha; Batt, Sarah M.; Besra, Kajelle Kaur; Xu, Wenqing; Bi, Lijun; Zhang, Xian'en; Guddat, Luke W.; Yang, Haitao; Wang, Quan; Besra, Gurdyal S.; Rao, Zihe.Cryo-EM snapshots of mycobacterial arabinosyltransferase complex EmbB(2)-AcpM(2).PROTEIN & CELL. 03 May 2020. 11(7):505-517.
- 27. Jin, Zhenming*; Du, Xiaoyu*; Xu, Yechun*; Deng, Yongqiang*; Liu, Meiqin*; Zhao, Yao; Zhang, Bing; Li, Xiaofeng; Zhang, Leike; Peng, Chao; Duan, Yinkai; Yu, Jing; Wang, Lin; Yang, Kailin; Liu, Fengjiang; Jiang, Rendi; Yang, Xinglou; You, Tian; Liu, Xiaoce; Yang, Xiuna; Bai, Fang; Liu, Hong; Liu, Xiang; Guddat, Luke W.; Xu, Wenqing; Xiao, Gengfu; Qin, Chengfeng; Shi, Zhengli; Jiang, Hualiang; Rao, Zihe; Yang, Haitao.Structure of M-pro from SARS-CoV-2 and discovery of its inhibitors.NATURE. 09 Apr 2020. 582(7811):289–293.
- 28. Wang, Hongyang*; Kim, Juhyun; Wang, Zhizhi; Yan, Xiao-Xue; Dean, Ann; Xu, Wenqing.Crystal structure of human LDB1 in complex with SSBP2.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 2020. 117(2):1042-1048.
- 29. Ma, Dan*; Wang, Zhizhi; Merrikh, Christopher N.; Lang, Kevin S.; Lu, Peilong; Li, Xin; Merrikh, Houra; Rao, Zihe; Xu, Wenqing.Crystal structure of a membrane-bound O-acyltransferase.NATURE. 11 Oct 2018. 562(7726):286-+.
- 30. Lu, Peilong*; Min, Duyoung; DiMaio, Frank; Wei, Kathy Y.; Vahey, Michael D.; Boyken, Scott E.; Chen, Zibo; Fallas, Jorge A.; Ueda, George; Sheffler, William; Mulligan, Vikram Khipple; Xu, Wenqing; Bowie, James U.; Baker, David.Accurate computational design of multipass transmembrane proteins.SCIENCE. 2018. 359(6379):1042-1046.
- 31. DaRosa, Paul A.*; Wang, Zhizhi*; Jiang, Xiaomo; Pruneda, Jonathan N.; Cong, Feng; Klevit, Rachel E.; Xu, Wenqing.Allosteric activation of the RNF146 ubiquitin ligase by a poly(ADP-ribosyl)ation signal.NATURE. 2015. 517(7533):223-U275.
- 32. Shen, Guobo*; Ke, Jiyuan*; Wang, Zhizhi; Cheng, Zhihong; Gu, Xin; Wei, Yuquan; Melcher, Karsten; Xu, H. Eric; Xu, Wenqing.Structural basis of the Norrin-Frizzled 4 interaction.CELL RESEARCH. 2015. 25(9):1078-1081.
- 33. Sun, Wei*; Zhu, Ye Julia; Wang, Zhizhi; Zhong, Qiang; Gao, Feng; Lou, Jizhong; Gong, Weimin; Xu, Wenqing.Crystal structure of the yeast TSC1 core domain and implications for tuberous sclerosis pathological mutations.NATURE COMMUNICATIONS. 2013. 4.
- 34. Wang, Zhizhi*; Michaud, Gregory A.; Cheng, Zhihong; Zhang, Yue; Hinds, Thomas R.; Fan, Erkang; Cong, Feng; Xu, Wenqing.Recognition of the iso-ADP-ribose moiety in poly(ADP-ribose) by WWE domains suggests a general mechanism for poly (ADP-ribosyl)ation-dependent ubiquitination.GENES & DEVELOPMENT. 2012. 26(3):235-240.
- 35. Morrone, Seamus*; Cheng, Zhihong; Moon, Randall T.; Cong, Feng; Xu, Wenqing.Crystal structure of a Tankyrase-Axin complex and its implications for Axin turnover and Tankyrase substrate recruitment.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 2012. 109(5):1500-1505.
- 36. Cheng, Zhihong*; Biechele, Travis; Wei, Zhiyi; Morrone, Seamus; Moon, Randall T.; Wang, Liguo; Xu, Wenqing.Crystal structures of the extracellular domain of LRP6 and its complex with DKK1.NATURE STRUCTURAL & MOLECULAR BIOLOGY. 2011. 18(11):1204.
- 37. Xu, Zheng*; Cetin, Bulent; Anger, Martin; Cho, Uhn Soo; Helmhart, Wolfgang; Nasmyth, Kim; Xu, Wenqing.Structure and Function of the PP2A-Shugoshin Interaction.MOLECULAR CELL. 2009. 35(4):426-441.
- 38. Liu, Jing*; Phillips, Bryan T.; Amaya, Maria F.; Kimble, Judith; Xu, Wenqing.The C. elegans SYS-1 protein is a bona fide beta-catenin.DEVELOPMENTAL CELL. 2008. 14(5):751-761.
- 39. Cho, Uhn Soo*; Xu, Wenqing.Crystal structure of a protein phosphatase 2A heterotrimeric holoenzyme.NATURE. 2007. 445(7123):53-57.
- 40. Cho, Uhn Soo*; Morrone, Seamus; Sablina, Anna A.; Arroyo, Jason D.; Hahn, William C.; Xu, Wenqing.Structural basis of PP2A inhibition by small t antigen.PLOS BIOLOGY. 2007. 5(8):1810-1819.
- 41. Sampietro, James*; Dahlberg, Caroline L.; Cho, Uhn Soo; Hinds, Thomas R.; Kimelman, David; Xu, Wenqing.Crystal structure of a beta-catenin/BCL9/Tcf4 complex.MOLECULAR CELL. 2006. 24(2):293-300.
- 42. Xing, Yi*; Clements, Wilson K.; Le Trong, Isolde; Hinds, Thomas R.; Stenkamp, Ronald; Kimelman, David; Xu, Wenqing.Crystal structure of a beta-Catenin/APC complex reveals a critical role for APC phosphorylation in APC function.MOLECULAR CELL. 2004. 15(4):523-533.
- 43. Xing, Yi*; Clements, Wilson K.; Kimelman, David; Xu, Wenqing.Crystal structure of a beta-catenin/axin complex suggests a mechanism for the beta-catenin destruction complex.GENES & DEVELOPMENT. 2003. 17(22):2753-2764.
- 44. Graham, Thomas A.*; Clements, Wilson K.; Kimelman, David; Xu, Wenqing.The crystal structure of the beta-catenin/ICAT complex reveals the inhibitory mechanism of ICAT.MOLECULAR CELL. 2002. 10(3):563-571.
- 45. Xu, Wenqing*; Harrison, Stephen C.; Eck, Michael J..Three-dimensional structure of the tyrosine kinase c-Src.NATURE. 1997. 385(6617):595-602.
- 46. Graham, Thomas A.*; Weaver, Carole; Mao, Feng; Kimelman, David; Xu, Wenqing.Crystal structure of a beta-catenin/Tcf complex.CELL. 2000. 103(6):885-896.
- 47. Xu, Wenqing*; Rould, Mark A; Jun, Susie; Desplan, Claude; Pabo, Carl O.CRYSTAL-STRUCTURE OF A PAIRED DOMAIN-DNA COMPLEX AT 2.5-ANGSTROM RESOLUTION REVEALS STRUCTURAL BASIS FOR PAX DEVELOPMENTAL MUTATIONS.CELL. 1995. 80(4):639-650.
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