刘万里 博士

研究员,博导,国家杰青,万人计划科技创新领军人才,树兰医学青年奖

2011.12 –   研究员,博导,清华大学,生命科学学院

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

 

● 研究兴趣、领域:

分子免疫学、细胞生物学、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、生物化学和生物物理研究手段,致力于淋巴细胞功能研究。正在开展的工作包括:(1)淋巴细胞活化的分子机制及调控机制的研究;(2)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)免疫记忆的分子机制;(4)淋巴细胞感受机械力的生物学;(5)病原微生物作用于淋巴细胞活化途径的免疫逃逸新机制;(6)构建基于上述知识的新型疫苗和新型抗体药物。

 

● 代表性论文:

代表性论文和综述(*表示通讯作者):

[1]  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.

[2]  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.

[3]  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)

[4]  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)

[5]  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)

[6]  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.

[7]  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.

[8]  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)

[9]  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.

[10]  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.

[11]  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.

[12]  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.

[13]  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.

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

[15]  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.

[16]  Shan Tang#, Zhengpeng Wan#, Yiren Gao#, Ji-Shen Zheng, Jing Wang, Yan-Yan Si, Xin Chen, Hai Qi, Lei Liu* and Wanli Liu* . Total chemical synthesis of photoactivatable proteins for light-controlled manipulation of antigen–antibody interactions. Chemical Science. 2016, 7:1891-1895.

[17]  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)

[18]  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.

[19]  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)

[20]  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)

[21]  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)

[22]  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)

[23]  Wanli Liu , Elizabeth Chen, XingWang Zhao, ZhengPeng Wan, YiRen Gao, Angel Davey, Eric Huang, Lijia Zhang, Jillian Crocetti, Gabriel Sandoval, M. Gordon Joyce, Carrie Miceli, Jan Lukszo, L. Aravind, Wojciech Swat, Joseph Brzostowski, and Susan K. Pierce. The scaffolding protein synapse associated protein 97 is required for enhanced signaling through isotype-switched IgG memory B cell receptors. Science Signaling. 2012, 5: ra54 1-13. (Faculty of 1000 recommended paper)

[24]  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)

[25]  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)

[26]  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 by Robert Brink)

[27]  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 and feature article commented by Michael Dustin)

[28]  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.

[29]  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 proteins. Eur J Immunol. 2005, 35:505-514.

[30]  Wanli Liu, Peng Zou, Jian Ding, Yun Lu and Ying-Hua Chen. Sequence comparison of the extracellular domain of M2 protein between human and avian influenza A virus provides new information for bivalent influenza vaccine design. Microbes and Infection. 2005, 7:171-177.

[31]  Wanli Liu, Peng Zou, ZQ Liu, Yun Lu, Jian Ding and Ying-Hua Chen. High epitope density in a single recombinant protein molecule of the extracellular domain of influenza A virus M2 protein significantly enhances protective immunity. Vaccine. 2004, 23: 366-371.


所有发表的论文,及其更新,请见:

https://www.ncbi.nlm.nih.gov/pubmed/?term=(Liu%2C+Wanli%5BAuthor%5D+AND+Tsinghua%5BAffiliation%5D)+OR+(Liu%2C+Wanli%5BAuthor%5D+AND+Pierce%2C+Susan+%5BAuthor%5D+AND+Rockville%5BAffiliation%5D)

或者

ORCID info (0000-0003-0395-2800):   https://orcid.org/0000-0003-0395-2800

或者

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

或者

清华学者:  http://rid.lib.tsinghua.edu.cn/scholar/654932

或者

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

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

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

● 联系方式:

Medical Science Bldg, RM-A103

Tsinghua University, Beijing, China, 100084

Tel: +86-10-62783617

电子邮箱:

LiuLab<********>tsinghua.edu.cn (Please replace<********>with@)

或者

LiuWanliLABATtsinghua<********>aliyun.com  (Please replace<********>with@)

或者

LiuWanli_TsinghuaU<********>126.com (Please replace<********>with@)

 

实验室网页:

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