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基础医学系

张林琦

履历

    2007- 至今  清华大学医学院教授,北京协和医学院兼职教授

               清华大学艾滋病综合研究中心主任

               清华大学全球健康与传染病研究中心主任

    1997-2007  美国洛克菲勒大学助理教授和副教授

    1993-1997  纽约大学博士后

    1988-1993  英国爱丁堡大学分子遗传学系博士,博士后

    1981-1985  北京师范大学生物系学士


研究领域与方向

艾滋病等人类重大病毒性传染病的致病机理,重点研究疾病进展过程中病毒与免疫系统相互作用关系,研发抗病毒药物、抗体和疫苗。通过解析多克隆和单克隆抗体的结构和功能,综合分析人体保护性抗体反应的组成特点,并利用结构生物学和系统生物学手段,理性设计优化单克隆抗体和疫苗,力争率先研发成功根治艾滋病的治疗策略和高效艾滋病疫苗。在研的其它方向包括埃博拉病毒,寨卡病毒,禽流感病毒,中东呼吸道冠状病毒等新发突发高致病性病毒。此外,担任清华大学医学院全球健康学科建设总协调人,负责相关学科人才引进、教学、科研和对外合作,积极推动新需求和新形势下的学科发展。


学术荣誉与奖励

    2016年当选为非洲科学院院士

    2015年获国家科技进步奖二等奖

    2008年获国家自然科学基金杰出青年基金

    2007年“新世纪百千万人才工程”国家级人选

    2003年获国家自然科学基金海外杰出青年基金


关键词

艾滋病毒,致病机理,抗体,疫苗,新发突发传染病,全球健康与传染病

代表性论文

1.    Wang H, Chen X, Wang D, Yao C, Wang Q, Xie J, Shi X, Xiang Y, Liu W, Zhang L. 2018. Epitope-focused immunogens against the CD4-binding site of HIV-1 envelope protein induce neutralizing antibodies against auto- and heterologous viruses. J Biol Chem 293:830-846. doi: 10.1074/jbc.M117.816447. Epub 2017 Nov 29.

2.    Yu L, Wang R, Gao F, Li M, Liu J, Wang J, Hong W, Zhao L, Wen Y, Yin C, Wang H, Zhang Q, Li Y, Zhou P, Zhang R, Liu Y, Tang X, Guan Y, Qin CF, Chen L, Shi X, Jin X, Cheng G, Zhang F, Zhang L. 2017. Delineating antibody recognition against Zika virus during natural infection. JCI Insight 2(12).93042. doi: 10.1172/jci.insight.93042.

3.    Shi B, Li J, Shi X, Jia W, Wen Y, Hu X, Zhuang F, Xi J, Zhang L. 2017. TALEN-Mediated Knockout of CCR5 Confers Protection Against Infection of Human Immunodeficiency Virus. J Acquir Immune Defic Syndr 74:229-241. doi: 10.1097/QAI.0000000000001190.

4.    Zhang Q, Gui M, Niu X, He S, Wang R, Feng Y, Kroeker A, Zuo Y, Wang H, Wang Y, Li J, Li C, Shi Y, Shi X, Gao GF, Xiang Y, Qiu X, Chen L, Zhang L. 2016. Potent neutralizing monoclonal antibodies against Ebola virus infection. Sci Rep 6:25856.

5.    Jin S, Ji Y, Wang Q, Wang H, Shi X, Han X, Zhou T, Shang H, Zhang L. 2016. Spatiotemporal hierarchy in antibody recognition against transmitted HIV-1 envelope glycoprotein during natural infection. Retrovirology 13:12.

6.    Zuo T, Sun J, Wang G, Jiang L, Zuo Y, Li D, Shi X, Liu X, Fan S, Ren H, Hu H, Sun L, Zhou B, Liang M, Zhou P, Wang X, Zhang L. 2015. Comprehensive analysis of antibody recognition in convalescent humans from highly pathogenic avian influenza H5N1 infection. Nat Commun 6:8855.

7.    Yu X, Zhang S, Jiang L, Cui Y, Li D, Wang D, Wang N, Fu L, Shi X, Li Z, Zhang L, Wang X. 2015. Structural basis for the neutralization of MERS-CoV by a human monoclonal antibody MERS-27. Sci Rep 5:13133.

8.    Jiang L, Wang N, Zuo T, Shi X, Poon KM, Wu Y, Gao F, Li D, Wang R, Guo J, Fu L, Yuen KY, Zheng BJ, Wang X, Zhang L. 2014. Potent Neutralization of MERS-CoV by Human Neutralizing Monoclonal Antibodies to the Viral Spike Glycoprotein. Sci Transl Med 6:234ra59.

9.    Wang N, Shi X, Jiang L, Zhang S, Wang D, Tong P, Guo D, Fu L, Cui Y, Liu X, Arledge KC, Chen YH, Zhang L, Wang X. 2013. Structure of MERS-CoV spike receptor-binding domain complexed with human receptor DPP4. Cell Res 23:986-93.

10.   Sun C, Chen Z, Tang X, Zhang Y, Feng L, Du Y, Xiao L, Liu L, Zhu W, Chen L, Zhang L. 2013. Mucosal priming with a replicating-vaccinia virus-based vaccine elicits protective immunity to simian immunodeficiency virus challenge in rhesus monkeys. J Virol 87:5669-77.

11.   Shang H, Xu J, Han X, Spero Li J, Arledge KC, Zhang L. 2012. HIV prevention: Bring safe sex to China. Nature 485:576-7.

12.   Guo D, Shi X, Arledge KC, Song D, Jiang L, Fu L, Gong X, Zhang S, Wang X, Zhang L. 2012. A single residue within the V5 region of HIV-1 envelope facilitates viral escape from the broadly neutralizing monoclonal antibody VRC01. J Biol Chem 287:43170-9.

13.   Zuo T, Shi X, Liu Z, Guo L, Zhao Q, Guan T, Pan X, Jia N, Cao W, Zhou B, Goldin M, Zhang L. 2011. Comprehensive analysis of pathogen-specific antibody response in vivo based on an antigen library displayed on surface of yeast. J Biol Chem 286:33511-9.

14.   Shang H, Han X, Shi X, Zuo T, Goldin M, Chen D, Han B, Sun W, Wu H, Wang X, Zhang L. 2011. Genetic and neutralization sensitivity of diverse HIV-1 env clones from chronically infected patients in China. J Biol Chem 286:14531-41.

15.   Liu Z, Shan M, Li L, Lu L, Meng S, Chen C, He Y, Jiang S, Zhang L. 2010. In Vitro Selection and Characterization of HIV-1 Variants with Increased Resistance to Sifuvirtide, a Novel HIV-1 Fusion Inhibitor. J Biol Chem 286:3277-87.

16.   Lu L, Jia M, Ma Y, Yang L, Chen Z, HO DD, Jiang Y, Zhang L. 2008. The Changing face of HIV in China. Nature 455:607-609.

17.   He Y, Xiao Y, Song H, Liang Q, Ju D, Chen X, Lu H, Jing W, Jiang S, Zhang L. 2008. Design and Evaluation of Sifuvirtide, a Novel HIV-1 Fusion Inhibitor. J Biol Chem 283:11126-34.

18.   Chen HY, Di Mascio M, Perelson AS, Ho DD, Zhang L. 2007. Determination of virus burst size in vivo using a single-cycle SIV in rhesus macaques. Proc Natl Acad Sci U S A 104:19079-84.

19.   Zhang L, Zhang F, Yu W, He T, Yu J, Yi CE, Ba L, Li W, Farzan M, Chen Z, Yuen KY, Ho D. 2006. Antibody responses against SARS coronavirus are correlated with disease outcome of infected individuals. J Med Virol 78:1-8.

20.   Lin HH, Shih YL, Liu YC, Lee SS, Huang CK, Chen YL, Chin C, Lai CH, Tsai HC, Guo YC, Zhang L. 2006. An epidemic of HIV type I CRF07_BC infection among injection drug users in Taiwan. J Acquir Immune Defic Syndr 42:248-55.

21.   Lin HH, Gaschen BK, Collie M, El-Fishaway M, Chen Z, Korber BT, Beatrice ST, Zhang L. 2006. Genetic characterization of diverse HIV-1 strains in an immigrant population living in New York City. J Acquir Immune Defic Syndr 41:399-404.

22.   Li C, Fu Y, Lu L, Ji W, Yu J, Hagedorn CH, Zhang L. 2006. Complete genomic sequences for hepatitis C virus subtypes 6e and 6g isolated from Chinese patients with injection drug use and HIV-1 co-infection. J Med Virol 78:1061-9.

23.   Liu L, Su B, Zhuang K, Tien P, Chen Z, Zhang L. 2005. Genetic Characterization of Full-Length HIV Type 1 Genomes from 3 Infected Paid Blood Donors in Henan, China. J Acquir Immune Defic Syndr 40:501-503.

24.   Arron ST, Ribeiro RM, Gettie A, Bohm R, Blanchard J, Yu J, Perelson AS, Ho DD, Zhang L. 2005. Impact of thymectomy on the peripheral T cell pool in rhesus macaques before and after infection with simian immunodeficiency virus. Eur J Immunol 35:46-55.

25.   Zhang L, Chen Z, Cao Y, Yu J, Li G, Yu W, Yin N, Mei S, Li L, Balfe P, He T, Ba L, Zhang F, Lin HH, Yuen MF, Lai CL, Ho DD. 2004. Molecular characterization of human immunodeficiency virus type 1 and hepatitis C virus in paid blood donors and injection drug users in china. J Virol 78:13591-9.

26.   Poles MA, Barsoum S, Yu W, Yu J, Sun P, Daly J, He T, Mehandru S, Talal A, Markowitz M, Hurley A, Ho D, Zhang L. 2003. Human immunodeficiency virus type 1 induces persistent changes in mucosal and blood gammadelta T cells despite suppressive therapy. J Virol 77:10456-67.

27.   Zhang L, Rowe L, He T, Chung C, Yu J, Yu W, Talal A, Markowitz M, Ho DD. 2002. Compartmentalization of surface envelope glycoprotein of human immunodeficiency virus type 1 during acute and chronic infection. J Virol 76:9465-73.

28.   Zhang L, Dailey PJ, Gettie A, Blanchard J, Ho DD. 2002. The liver is a major organ for clearing simian immunodeficiency virus in rhesus monkeys. J Virol 76:5271-3.

29.   Zhang L, Chung C, Hu BS, He T, Guo Y, Kim AJ, Skulsky E, Jin X, Hurley A, Ramratnam B, Markowitz M, Ho DD. 2000. Genetic characterization of rebounding HIV-1 after cessation of highly active antiretroviral therapy. J Clin Invest 106:839-45.

30.   Ho DD, Zhang L. 2000. HIV-1 rebound after anti-retroviral therapy. Nat Med 6:736-7.

31.   Zhang L, Ramratnam B, Tenner-Racz K, He Y, Vesanen M, Lewin S, Talal A, Racz P, Perelson AS, Korber BT, Markowitz M, Ho DD. 1999. Quantifying residual HIV-1 replication in patients receiving combination antiretroviral therapy. N Engl J Med 340:1605-13.

32.   Zhang L, Lewin SR, Markowitz M, Lin HH, Skulsky E, Karanicolas R, He Y, Jin X, Tuttleton S, Vesanen M, Spiegel H, Kost R, van Lunzen J, Stellbrink HJ, Wolinsky S, Borkowsky W, Palumbo P, Kostrikis LG, Ho DD. 1999. Measuring recent thymic emigrants in blood of normal and HIV-1-infected individuals before and after effective therapy. J Exp Med 190:725-32.

33.   Zhang L, Dailey PJ, He T, Gettie A, Bonhoeffer S, Perelson AS, Ho DD. 1999. Rapid clearance of simian immunodeficiency virus particles from plasma of rhesus macaques. J Virol 73:855-60.

34.   Zhang L, He T, Talal A, Wang G, Frankel SS, Ho DD. 1998. In vivo distribution of the human immunodeficiency virus/simian immunodeficiency virus coreceptors: CXCR4, CCR3, and CCR5. J Virol 72:5035-45.

35.   Zhang L, He T, Huang Y, Chen Z, Guo Y, Wu S, Kunstman KJ, Brown RC, Phair JP, Neumann AU, Ho DD, Wolinsky SM. 1998. Chemokine coreceptor usage by diverse primary isolates of human immunodeficiency virus type 1. J Virol 72:9307-12.

36.   Zhang L, Huang Y, Yuan H, Tuttleton S, Ho DD. 1997. Genetic characterization of vif, vpr, and vpu sequences from long-term survivors of human immunodeficiency virus type 1 infection. Virology 228:340-9.

37.   Zhang L, Huang Y, Yuan H, Chen BK, Ip J, Ho DD. 1997. Identification of a replication-competent pathogenic human immunodeficiency virus type 1 with a duplication in the TCF-1alpha region but lacking NF-kappaB binding sites. J Virol 71:1651-6.

38.   Zhang L, Huang Y, Yuan H, Chen BK, Ip J, Ho DD. 1997. Genotypic and phenotypic characterization of long terminal repeat sequences from long-term survivors of human immunodeficiency virus type 1 infection. J Virol 71:5608-13.

39.   Zhang L, Diaz RS, Ho DD, Mosley JW, Busch MP, Mayer A. 1997. Host-specific driving force in human immunodeficiency virus type 1 evolution in vivo. J Virol 71:2555-61.

40.   Zhang L, Carruthers CD, He T, Huang Y, Cao Y, Wang G, Hahn B, Ho DD. 1997. HIV type 1 subtypes, coreceptor usage, and CCR5 polymorphism. AIDS Res Hum Retroviruses 13:1357-66.

41.   Zhang L, Huang Y, He T, Cao Y, Ho DD. 1996. HIV-1 subtype and second-receptor use. Nature 383:768.

42.   Zhang L, MacKenzie P, Cleland A, Holmes EC, Brown AJ, Simmonds P. 1993. Selection for specific sequences in the external envelope protein of human immunodeficiency virus type 1 upon primary infection. J Virol 67:3345-56.

43.   Zhang L, Simmonds P, Ludlam CA, Brown AJ. 1991. Detection, quantification and sequencing of HIV-1 from the plasma of seropositive individuals and from factor VIII concentrates. Aids 5:675-81.


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Phone: +86-10-62788131

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