生命科学联合中心

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刘万里

刘万里博士

长聘终身教授（tenured full professor），教育部长江学者特聘教授，基金委杰青，科技部万人计划领军人才，药明康德生命化学杰出成就奖

2011.12 – 研究员，博导，清华大学，生命科学学院，免疫学研究所

2007 – 2011 博士后美国国立卫生研究院（NIH），过敏与传染病研究所（NIAID）

2005 – 2007 博士后美国加州大学旧金山分校（UCSF），微生物与免疫学系

2001 – 2005 博士清华大学，生物科学与技术系

1997 – 2001 学士中国农业大学，生物学院

科研领域与方向

分子免疫学、细胞生物学、分子疫苗学。应用高速高分辨率的活细胞单分子荧光成像技术，并结合传统的免疫学、分子细胞、生物化学和生物物理研究手段，致力于B淋巴细胞机制和功能研究：（1）B淋巴细胞免疫识别和免疫活化的分子机制及调控机制的研究；（2）B淋巴细胞异常活化导致的自身免疫疾病及淋巴癌和白血病的研究；（3）B淋巴细胞生成-储存-读取长效型抗体记忆的研究；（4）B淋巴细胞依赖机械力感知调控免疫活化和功能的研究；（5）病原微生物作用于B淋巴细胞早期活化途径的免疫逃逸的研究；（6）整合攻关基于上述研究结果的新型疫苗和新型药物。

代表性论文和综述（*表示通讯作者）：

[1] Bing Yang^#, Zhen Zhang^#, Xiangjun Chen^#, Xu-Yan Wang, Shishang Qin, Liaoqi Du, Changjiang Yang, Liyu Zhu, Wenbo Sun, Yongjie Zhu, Qinwen Zheng, Shidong Zhao, Quan Wang, Long Zhao, Yilin Lin, Jinghe Huang, Fan Wu, Lu Lu, Fei Wang, Wenjie Zheng, Xiao-Hua Zhou, Xiaozhen Zhao, Ziye Wang, Sun Xiao-Lin, Yingjiang Ye, Shan Wang, Zhanguo Li, Hai Qi, Zemin Zhang, Dong-Ming Kuang, Lei Zhang, Zhanlong Shen*, Wanli Liu*. An Asian-specific variant in human IgG1 represses colorectal tumorigenesis by shaping the tumor microenvironment. J Clin Invest. 2022, e153454. doi: 10.1172/JCI153454. (featured article with a preview commentary)

[2] Jing Chen^#, Xiaochen Zhang^#, Liping Li^#, Xianqiang Ma, Chunxiao Yang, Zhaodi Liu, Chenyang Li, Maria J. Fernandez-Cabezudo, Basel K. al-Ramadi, Chuan Wu, Weishan Huang, Yong Zhang*, Yonghui Zhang*, Wanli Liu*. Farnesyl pyrophosphate is a new danger signal inducing acute cell death. PLoS Biology. 2021, 19:e3001134. doi: 10.1371/journal.pbio.3001134. (featured article with an editor’s digest)

[3] Wanli Liu*, Pavel Tolar*, Wenxia Song*, Tae Jin Kim*. B cell receptor signaling and B cell activation. Frontiers in Immunology. 2020, 11:45. doi: 10.3389/fimmu.2020.00045. (Review)

[4] Yangyang Feng, Yu Wang, Shaocun Zhang, Kabeer Haneef, Wanli Liu*. Structural and immunogenomic insights for B cell receptor activation. Journal of Genetics and Genomics. 2020, 47:27-35. (Review)

[5] Ji Gao^#, Juan He^#, Qingwen Wang*, Wanli Liu*. Monoclonal antibodies: Emergence, present and outlook. Chinese Science Bulletin. 2020, 65:3085-3090. (Review)

[6] Samina Shaheen, Zhengpeng Wan, Kabeer Haneef, Yingyue Zeng, Wang Jing, Wanli Liu*. B cell mechanosensing: A mechanistic overview. Advances Immunology. 2019, 144:23-63. (Review)

[7] Chenguang Xu, Zhengpeng Wan, Samina Shaheen, Jing Wang, Zhiyong Yang, Wanli Liu*. A PI(4,5)P2 derived “gasoline engine model” for the sustained B cell receptor activation. Immunological Reviews. 2019, 291:75-90. (Review)

[8] Zhengpeng Wan, Samina Shaheen, Alicia Chau, Wanli Liu*. Imaging: Gear up for Mechano-Immunology. Cellular Immunology. 2019, 103926. doi: 10.1016/j.cellimm.2019.103926. (Review)

[9] Feng Lin^#, Junyi Wang^#, Yingyue Zeng, Chunyang Xiong*, Wanli Liu*. Traction Force-mediated B Cell Activation: How and Why. Sci China Life Sci. 2019, 62:971–973. (Review)

[10] Xingwang Zhao^#, Hengyi Xie^#, Meng Zhao^#, Asma Ahsan, Xinxin Li, Fei Wang, Junyang Yi, Zhiyong Yang, Chuan Wu, Indu Raman, Quan-Zhen Li*, Tae Jin Kim*, Wanli Liu*. Fc receptor-like 1 intrinsically recruits c-Abl to enhance B cell activation and function. Science Advances. 2019, 5, eaaw0315, DOI: 10.1126/sciadv.aaw0315

[11] Zhixun Shen^#, Sichen Liu^#, Xinxin Li^#, Zhengpeng Wan, Youxiang Mao, Chunlai Chen, Wanli Liu*. Conformational change within the extracellular domain of B cell receptor in B cell activation upon antigen binding. eLife. 2019, 8, doi: 10.7554/eLife.42271.

[12] Chenguang Xu^#, Yan Fang^#, Zhiyong Yang, Yukai Jing, Yonghui Zhang, Chaohong Liu*, Wanli Liu*. MARCKS regulates tonic and chronic active B cell receptor signaling. Leukemia. 2019, 33:710-729.

[13] Wei Hu^#, Yong Zhang^#, Xiaolin Sun^#, Tongtong Zhang, Liling Xu, Hengyi Xie, Zhanguo Li, Wanli Liu*, Jizhong Lou*, Wei Chen*. FcγRIIB-I232T polymorphic change allosterically suppresses ligand binding. eLife. 2019, 8, doi: 10.7554/eLife.46689.

[14] Yukai Jing^#, Danqing Kang^#, Luyao Liu, Huang Huang, Anwei Chen, Lu Yang, Panpan Jiang, Na Li, Heather Miller, Zheng Liu, Xiaofei Zhu, Jun Yang, Xiaochuan Wang, Jinqiao Sun*, Zhiping Liu*, Wanli Liu*, Xinyuan Zhou*, Chaohong Liu*. Dock2 couples with LEF-1 to regulate the expression of CD21 and B cell differentiation. J Allergy Clin Immunol. 2019 Jul 29. pii: S0091-6749(19)30829-2. doi: 10.1016/j.jaci.2019.05.041.

[15] Yonghui Sun^#, Ning Ding^#, Yuqin Song^#, Zimo Yang, Wanli Liu*, Jun Zhu* and Yu Rao*. Degradation of Bruton's tyrosine kinase mutants by PROTACs for potential treatment of ibrutinib-resistant non-Hodgkin lymphomas. Leukemia. 2019, doi: 10.1038/s41375-019-0440-x.

[16] Xiangjun Chen, Xiaolin Sun^#, Wei Yang^#, Bing Yang^#, Xiaozhen Zhao, Shuting Chen1, Lili He, Hui Chen, Changmei Yang, Le Xiao, Zai Chang, Jianping Guo, Jing He, Fuping Zhang, Fang Zheng, Zhibin Hu, Zhiyong Yang, Jizhong Lou, Wenjie Zheng, Hai Qi, Chenqi Xu, Hong Zhang, Hongying Shan, Xu-jie Zhou, Qingwen Wang, Yi Shi, Luhua Lai, Zhanguo Li *, Wanli Liu*. An autoimmune disease variant of IgG1 modulates B-cell activation and differentiation. Science. 2018, 362:700-705. (Nature Reviews Rheumatology, Research Highlights)

[17] Yun Xia^#, Yonghua Xie^#, Zhengsen Yu^#, Hongying Xiao, Guimei Jiang, Xiaoying Zhou, Yunyun Yang, Xin Li, Meng Zhao, Liping Li, Mingke Zheng, Shuai Han, Zhaoyun Zong, Xianbin Meng, Haiteng Deng, Huahu Ye, Yunzhi Fa, Haitao Wu, Eric Oldfield, Xiaoyu Hu, Wanli Liu*, Yan Shi*, Yonghui Zhang*. The mevalonate pathway is a druggable target for vaccine adjuvant discovery. Cell. 2018, 175:1059-1073. (Nature Reviews Immunology, Research Highlights)

[18] Junyi Wang^#, Feng Lin^#, Zhengpeng Wan, Xiaolin Sun, Yun Lu, Jianyong Huang, Fei Wang, Yingyue Zeng, Ying-Hua Chen, Yan Shi, Wenjie Zheng, Zhanguo Li, Chunyang Xiong*, Wanli Liu*. Profiling the origin, dynamics, and function of traction force in B cell activation. Science Signaling. 2018, 11. pii: eaai9192. doi: 10.1126/scisignal.aai9192. (Cover story)

[19] Zhengpeng Wan, Chenguang Xu^#, Xiangjun Chen^#, Hengyi Xie^#, Zongyu Li^#, Jing Wang^#, Xingyu Ji, Haodong Chen, Qinghua Ji, Samina Shaheen, Yang Xu, Fei Wang, Zhuo Tang, Ji-Shen Zheng, Wei Chen, Jizhong Lou, Wanli Liu*. PI(4,5)P2 determines the threshold of mechanical force-induced B cell activation. J Cell Biol. 2018, 217:2565-2582.

[20] Yonghui Sun^#, Xingwang Zhao^#, Ning Ding^#, Hongying Gao^#, Yue Wu, Yiqing Yang, Meng Zhao, Jinseok Hwang, Yuqin Song, Wanli Liu*, Yu Rao*. PROTAC-induced BTK degradation as a novel therapy for mutated BTK C481S induced ibrutinib-resistant B-cell malignancies. Cell Research. 2018, 28:779-781.

[21] Chenguang Xu, Hengyi Xie, Xingdong Guo, Haipeng Gong, Lei Liu, Hai Qi, Chenqi Xu, Wanli Liu*. A PIP2-derived amplification loop fuels the sustained initiation of B cell activation. Science Immunology. 2017, 2. pii: eaan0787. doi: 10.1126/sciimmunol.aan0787. (Science Signaling, Editor’s choice)

[22] Jing Wang, Liling Xu, Samina Shaheen, Sichen Liu, Wenjie Zheng, Xiaolin Sun, Zhanguo Li, Wanli Liu*. Growth of B cell receptor microclusters is regulated by PIP2 and PIP3 equilibrium and Dock2 recruitment and activation. Cell Reports. 2017, 21:2541-2557.

[23] Samina Shaheen^#, Zhengpeng Wan^#, Zongyu Li^#, Alicia Chau, Xinxin Li, Shaosen Zhang, Yang Liu, Junyang Yi, Yingyue Zeng, Jing Wang, Xiangjun Chen, Liling Xu, Wei Chen, Fei Wang, Yun Lu, Wenjie Zheng, Yan Shi, Xiaolin Sun, Zhanguo Li, Chunyang Xiong, Wanli Liu*. Substrate stiffness governs the initiation of B cell activation by the concerted signaling of PKCβ and focal adhesion kinase. eLife. 2017, 6:e23060, doi: 10.7554/eLife.23060.

[24] Yingjia Chen^#, Fanlei Hu^#, Xuejiao Dong, Meng Zhao, Jing Wang, Xiaolin Sun, Tae Jin Kim*, Zhanguo Li*, Wanli Liu*. SHIP-1 deficiency in AID+ B cells leads to the impaired function of B10 cells with spontaneous autoimmunity. J Immunol. 2017, 199:3063-3073.

[25] Jingjing Liang^#, Jun Lyu^#, Meng Zhao, Dan Li, Mingzhu Zheng, Yan Fang, Fangzhu Zhao, Jun Lou, Chuansheng Guo, Lie Wang, Di Wang, Wanli Liu*, Linrong Lu*. Tespa1 regulates T cell receptor-induced calcium signals by recruiting inositol 1, 4, 5-trisphosphate receptors. Nature Communications. 2017, 8:15732. doi: 10.1038/ncomms15732.

[26] Liling Xu^#, Mengdie Xia^#, Jun Guo^#, Xiaolin Sun^#, Hua Li, Chenguang Xu, Xiaomei Gu, Haowen Zhang, Junyang Yi, Yan Fang, Hengyi Xie, Jing Wang, Zhixun Shen, Boxin Xue, Yujie Sun, Tobias Meckel, Ying-Hua Chen, Zhibin Hu, Zhanguo Li*, Chenqi Xu*, Haipeng Gong*, Wanli Liu*. Impairment on the lateral mobility induced by structural changes underlies the functional deficiency of the lupus-associated polymorphism FcγRIIB-T232. J Exp Med. 2016, 213:2707-2727.

[27] Wanli Liu*, Haopeng Wang, Chenqi Xu*. Antigen receptor nanoclusters: small units with big functions. Trends ln Immunology. 2016, 37:680-689. (Review)

[28] Jing Wang^#, Shan Tang^#, Zhengpeng Wan, Yiren Gao, Yiyun Cao, Junyang Yi, Yanyan Si, Haowen Zhang, Lei Liu* and Wanli Liu*. Utilization of a photoactivatable antigen system to examine B cell probing termination and the B cell receptor sorting mechanisms during B cell activation. PNAS. 2016, 113:E558-567.

[29] Zhengpeng Wan, Xiangjun Chen, Haodong Chen, Qinghua Ji, Yingjia Chen, Jing Wang, Yiyun Cao, Fei Wang, Jizhong Lou, Zhuo Tang and Wanli Liu*. The activation of IgM- or isotype-switched IgG- and IgE-BCR exhibits distinct mechanical force sensitivity and threshold. eLife. 2015, 4:e06925 (Faculty of 1000 recommended paper)

[30] Xiangjun Chen^#, Weiling Pan^#, Yinqiang Sui, Hua Li, Xiaoshan Shi, Xingdong Guo, Hai Qi, Chenqi Xu* and Wanli Liu*. Acidic phospholipids govern the enhanced activation of IgG-B cell receptor. Nature Communications. 2015, 6:8552.

[31] Yingyue Zeng, Junyang Yi, Zhengpeng Wan, Kai Liu, Ping Song, Alicia Chau, Fei Wang, Zai Chang, Weidong Han, Wenjie Zheng, Ying-Hua Chen*, Chunyang Xiong* and Wanli Liu*. Substrate stiffness regulates B-cell activation, proliferation, class switch and T-cell-independent antibody responses in vivo. Eur J Immunol. 2015, 45:1621-1634. (Feature article with a preview)

[32] Liling Xu, Gen Li, Jing Wang, Yilin Fan, Zhengpeng Wan, Shaosen Zhang, Samina Shaheen, Jing Li, Li Wang, Cai Yue, Yan Zhao, Fei Wang, Joseph Brzostowski, Yinghua Chen*, Wenjie Zheng* and Wanli Liu*. Through an ITIM-independent mechanism the FcgRIIB blocks B cell activation by disrupting the colocalized microclustering of the BCR and CD19. J Immunol. 2014, 192:5179-91. (Faculty of 1000 recommended paper)

[33] Yinsheng Xu^#, Liling Xu^#, Meng Zhao, Chenguang Xu, Yilin Fan, Susan K. Pierce* and Wanli Liu*. No receptor stands alone: IgG B cell receptor intrinsic and extrinsic mechanisms contribute to antibody memory. Cell Research. 2014, 24:651-64. (Review)

[34] Zhengpeng Wan, Shaosen Zhang, Yilin Fan, Kai Liu, Feng Du, Angel M. Davey, Huiyuan Zhang, Weidong Han, Chunyang Xiong and Wanli Liu*. B cell activation is regulated by the stiffness properties of the substrate presenting the antigens. J Immunol. 2013, 190:4661-4675. (Faculty of 1000 recommended paper)

[35] Susan K. Pierce and Wanli Liu. The tipping points in the initiation of B cell signaling: how small changes make big differences. Nature Reviews Immunology. 2010, 10:767-777. (Cover Review)

[36] Wanli Liu, Hae Won Sohn, Pavel Tolar, Susan K. Pierce. It's all about change: the antigen-driven initiation of B-cell receptor signaling. Cold Spring Harb Perspect Biol. 2010, 2:a002295. (Review)

[37] Wanli Liu, Tobias Meckel, Pavel Tolar, Hae Won Sohn, Susan K. Pierce. Intrinsic properties of immunoglobulin IgG1 isotype-switched B cell receptors promote microclustering and the initiation of signaling. Immunity. 2010, 32:778-789. (Feature article with a preview)

[38] Wanli Liu, Tobias Meckel, Pavel Tolar, Hae Won Sohn, Susan K. Pierce. Antigen affinity discrimination is an intrinsic function of the B cell receptor. J Exp Med. 2010, 207:1095-1111. (Cover story with a preview)

[39] Wanli Liu, Tobias Meckel, Pavel Tolar, Hae Won Sohn, Susan K. Pierce. Antigen-induced oligomerization of the B cell receptor is an early target of Fc gamma RIIB inhibition. J Immunol. 2010, 184:1977-1989. (‘In This Issue’ featured article)

[40] Wanli Liu and Ying-Hua Chen. High epitope density in single protein molecule significantly enhanced antigenicity as well as immunogenicity: a novel strategy for modern vaccine development and a preliminary investigation about B cell discrimination of monomeric protein

s. Eur J Immunol. 2005, 35:505-514.

完整论文列表及其更新：

https://pubmed.ncbi.nlm.nih.gov/?term=wanli+liu%2C+tsinghua&sort=date

https://scholar.google.com/citations?user=UE-r4yYAAAAJ&hl=en&oi=ao

https://www.researchgate.net/profile/Wanli_Liu3

https://loop.frontiersin.org/people/99619/overview

https://www.scopus.com/authid/detail.uri?authorId=35213378100

https://orcid.org/0000-0003-0395-2800

http://rid.lib.tsinghua.edu.cn/scholar/654932

实验室网页：

https://www.labxing.com/wanli-liu-lab