更新时间：2024-09-21 10:06
刘万里，毕业于中国农业大学、清华大学，博士学位，清华大学生命学院研究员，博士生导师。
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 加州大学旧金山分校（陈晓薇），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
清华大学刘万里实验室的研究兴趣主要在分子免疫学、细胞生物学和疫苗学。我们致力于B淋巴细胞识别特异性抗原而引发的细胞活化的分子机制及其调控机制的研究；我们也致力于B细胞活化的调节失控引发的自身免疫疾病以及淋巴癌的研究。同时我们希望发现病原微生物作用于B细胞活化过程的免疫逃逸新机制；我们也希望通过对B细胞活化机制的研究而构思新型的新型冠状病毒疫苗设计理念。
我们的研究手段将依赖新型的高速高分辨率的活细胞单分子荧光成像技术，并结合传统的分子生物学、细胞生物学、生物化学实验技术。我们的研究模型包括实验室B细胞系、相关的转基因小鼠及基因敲除小鼠的成熟B细胞、人外周血B细胞等。
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新型冠状病毒疫苗和新型抗体药物。
论文和综述（*表示通讯作者）：
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.
Wanli Liu*, Haopeng Wang, Chenqi Xu*. Antigen Receptor Nanoclusters: Small Units with Big Functions. Trends ln Immunology. 2016, 37:680-689.
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, doi:10.1073/pnas.1517612113.
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. DOI: 10.1039/C5SC03404C.
Xiangjun Chen, Weiling pan, Yinqiang Sui, Hua Li, Xiaoshan Shi, Xingdong Guo, Hai Qi, Chenqi Xu*, Wanli Liu*. Acidic phospholipids govern the enhanced activation of IgG-B cell receptor. Nature Communications. 2015, 6:8552. doi: 10.1038/ncomms9552.
Zhengpeng Wan, Xiangjun Chen, Haodong Chen, Qinghua Ji, Yingjia Chen, Jing Wang, Yiyun Cao, Fei Wang, Jizhong Lou, Zhuo Tang, Wanli Liu*. The activation of IgM- or isotype-switched IgG- and IgE-BCR exhibits distinct mechanical force sensitivity and threshold. Elife. 2015 doi: 10.7554/eLife.06925. (Faculty of 1000 recommended paper)
Xiangjun Chen, Gen Li, Zhengpeng Wan, Ce Liu, Yingyue Zeng, Wanli Liu*. How B cells remember? A sophisticated cytoplasmic tail of mIgG is pivotal for the enhanced transmembrane signaling of IgG-switched memory B cells. Progress in Biophysics and Molecular Biology. 2015, 118:89-94. (Review)
Liling Xu, Arturs Auzins, Xiaolin Sun, Yinsheng Xu, Fiona Harnischfeger, Yun Lu, Juan Qiao, Zhanguo Li, Ying-Hua Chen*, Wenjie Zheng*, Wanli Liu*. The synaptic recruitment of lipid rafts is dependent on CD19-pi3k module and cytoskeleton remodeling molecules. J Leukoc Bi奥林匹克里昂女子足球队 2015, 98:223-234.
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*, 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 commented by Dr. Andrew M. 卓定)
Ce Liu, Xingwang Zhao, Liling Xu, Junyang Yi, Samina Shaheen, Weidong Han, Fei Wang, Wenjie Zheng, Chenqi Xu, Wanli Liu*. A negative-feedback 函数 of PKCβ in the formation and accumulation of signaling-active B cell receptor microclusters within B cell immunological synapse. J Leukoc Biol. 2015 97:887-900.
YinSheng Xu, JunYang Yi, YiRen Gao, Ce Liu, LiLing Xu, WanLi Liu*. Molecular Mechanism of B Lymphocyte Activation and the Associated Diseases. Scientia Sinica Vitae, 2014, 44:985-998. (Review in Chinese language)
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*, 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)
Guoliang Zhang, Huiyuan Zhang, Yuan Gao, Ran Tao, Lijun Xin, Junyang Yi, Fuyou Li, Wanli Liu* and Juan Qiao*. Near-Infrared-Emitting Iridium(III) Complexes as Phosphorescent Dyes for Live Cell Imaging. Organometallics, 2014, 33:61−68.
Yinsheng Xu, Meng Zhao, 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)
Zhengpeng Wan, Shaosen Zhang, Yilin Fan, Kai Liu, Feng Du, Angel M. Davey, Huiyuan Zhang, Weidong Han, Chunyang Xiong, 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)
Shaosen Zhang, Liling Xu, Xingwang Zhao, Xin Chen, Zhengpeng Wan, Yinsheng Xu, Wanli Liu*. A new and robust method of tethering IgG surrogate antigens on lipid bilayer membranes to facilitate the TIRFM based live cell and single molecule imaging experiments. Plos One. 2013, 8:e63735.
Zhengpeng Wan, Wanli Liu*. The growth of B cell receptor microcluster is a universal response of B cells encountering antigens with different motion features. Protein \u0026 Cell. 2012 3:545-558.
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)
Angel Davey1, Wanli Liu1, Hae Won Sohn1, Joseph Brzostowski1 and Susan K. Pierce. Understanding the initiation of B cell signaling through live cell imaging. Methods in Enzymology. 2012, 506:265-290. (1 indicates co-first author)
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)
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)
Wanli Liu, Tobias Meckel, Pavel Tolar, Hae Won Sohn, Susan K. Pierce. Antigen affinity discrimination is an intrinsic 函数 of the B cell 捕手 J Exp Med. 2010, 207:1095-1111. (COVERSTORY and feature article commented by Michael Dustin)
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” article by Christiana N. Fogg)
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)
2017年11月18日，清华大学生命学院刘万里研究组在《科学》旗下免疫学子刊《科学·免疫学》(Science Immunology)期刊发表了题为《源自磷脂肌醇4,5-二磷酸的正反馈环路持续性驱动B细胞免疫活化》(A PIP2 derived amplification loop fuels the sustained initiation of B cell activation)的研究论文。报道B细胞免疫突触中具有时空特异性的磷脂酰肌醇4,5-二磷酸水解与再生代谢作用形成的正反馈环路(feed forward loop)，有力地促进抗原受体(BCR)跨膜信号转导和细胞活化的新机制，为相关疾病研究提供了新的理论依据。
刘万里研究员为本文的通讯作者，清华大学生命科学学院博士生许晨光为本文的第一作者。本研究得到了中科院上海生物化学与细胞生物学研究所许琛琦教授，清华大学医学院祁海教授、化学系刘磊教授和生命学院龚海鹏教授等的大力支持。该研究得到国家中华人民共和国国家自然科学基金委员会、科技部和青年以及清华大学免疫学研究所的支持。论文链接：http://immunology.sciencemag.org/content/2/17/eaan0787
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