劉萬里，畢業(yè)于中國農(nóng)業(yè)大學、清華大學，博士學位，清華大學生命學院研究員，博士生導師。
個人經(jīng)歷
2011.12?–???研究員，博導，清華大學，生命科學學院
2007?–?2011?博士后?美國國立衛(wèi)生研究院（NIH），過敏與傳染病研究所（NIAID）
2005?–?2007?博士后?加州大學舊金山分校（陳曉薇），微生物與免疫學系
2001?–?2005?博士???清華大學，生物科學與技術(shù)系
1997?–?2001?學士??中國農(nóng)業(yè)大學，生物學院
研究方向
研究興趣
清華大學劉萬里實驗室的研究興趣主要在分子免疫學、細胞生物學和疫苗學。我們致力于B淋巴細胞識別特異性抗原而引發(fā)的細胞活化的分子機制及其調(diào)控機制的研究；我們也致力于B細胞活化的調(diào)節(jié)失控引發(fā)的自身免疫疾病以及淋巴癌的研究。同時我們希望發(fā)現(xiàn)病原菌作用于B細胞活化過程的免疫逃逸新機制；我們也希望通過對B細胞活化機制的研究而構(gòu)思新型的新型冠狀病毒疫苗設計理念。
研究手段
我們的研究手段將依賴新型的高速高分辨率的活細胞單分子熒光成像技術(shù)，并結(jié)合傳統(tǒng)的分子生物學、細胞生物學、生物化學實驗技術(shù)。我們的研究模型包括實驗室B細胞系、相關(guān)的轉(zhuǎn)基因小鼠及基因敲除小鼠的成熟B細胞、人外周血B細胞等。
科研領(lǐng)域與方向
分子免疫學、細胞生物學、疫苗學。應用高速高分辨率的活細胞單分子熒光成像技術(shù)，并結(jié)合傳統(tǒng)的免疫學、生物化學和生物物理研究手段，致力于淋巴細胞功能研究。
正在開展的工作包括：
（1）淋巴細胞活化的分子機制及調(diào)控機制的研究；
（2）淋巴細胞異?；罨瘜е碌淖陨砻庖呒膊〖傲馨桶┖?a href="/hebeideji/7218812787295895552.html">白血病的研究；
（3）免疫記憶的分子機制；
（4）淋巴細胞感受機械力的生物學；
（5）病原菌作用于淋巴細胞活化途徑的免疫逃逸新機制；
（6）構(gòu)建基于上述知識的新型新型冠狀病毒疫苗和新型抗體藥物。
發(fā)表論文
論文和綜述（*表示通訊作者）：
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*.?抗原?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?抗原?system?to?examine?B?cell?probing?termination?and?the?B?cell?receptor?sorting?mechanisms?during?B?細胞?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?抗原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?細胞骨架?remodeling?molecules.?J?Leukoc?Biol.?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?函數(shù)?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?銥(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?&?細胞?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.?抗原?affinity?discrimination?is?an?intrinsic?函數(shù)?of?the?B?cell?receptor.?J?Exp?Med.?2010,?207:1095-1111.?(Cover?story?and?feature?article?commented?by?Michael?Dustin)
Wanli?Liu,?Tobias?Meckel,?Pavel?Tolar,?Hae?Won?Sohn,?Susan?K.?Pierce.?抗原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?抗原driven?initiation?of?B-cell?receptor?signaling.?Cold?Spring?Harb?Perspect?Biol.?2010,?2:a002295.?(Review)
2017年11月18日，清華大學清華大學生命科學學院劉萬里研究組在《科學》旗下免疫學子刊《科學·免疫學》(Science?Immunology)期刊發(fā)表了題為《源自磷脂肌醇4,5-二磷酸的正反饋環(huán)路持續(xù)性驅(qū)動B細胞免疫活化》(A?PIP2?derived?amplification?loop?fuels?the?sustained?initiation?of?B?cell?activation)的研究論文。報道B細胞免疫突觸中具有時空特異性的磷脂酰肌醇4,5-二磷酸水解與再生代謝作用形成的正反饋環(huán)路(feed?forward?loop)，有力地促進抗原受體(BCR)跨膜信號轉(zhuǎn)導和細胞活化的新機制，為相關(guān)疾病研究提供了新的理論依據(jù)。
劉萬里研究員為本文的通訊作者，清華大學生命科學學院博士生許晨光為本文的第一作者。本研究得到了中科院上海生物化學與細胞生物學研究所許琛琦教授，清華大學醫(yī)學院祁海教授、化學系劉磊教授和生命學院龔海鵬教授等的大力支持。該研究得到國家中華人民共和國國家自然科學基金委員會、科技部和青年以及清華大學免疫學研究所的支持。論文鏈接：http://immunology.sciencemag.org/content/2/17/eaan0787
獲得榮譽
2020年8月，入選第十六屆中國青年科技獎獲獎名單。
2019年12月，第十三屆藥明康德生命化學杰出成就獎。
參考資料 >
中國科學技術(shù)協(xié)會 組織人才 關(guān)于第十六屆中國青年科技獎獲獎人選的公示.中國科學技術(shù)協(xié)會.2020-08-31
第十三屆“藥明康德生命化學研究獎”在京揭曉-新華網(wǎng).新華網(wǎng).2021-12-17