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杰出青年科学基金获得者

高光侠  博士 研究员 博士生导师  

国家“杰出青年基金”、“创新研究群体”学术带头人、人事部“百千万人才计划”获得者
中科院感染与免疫重点实验室主任,研究组长 

研究方向:病毒与宿主相互作用的分子机制

电子邮件:gaogx@ibp.ac.cn

电       话:010-64888545

通讯地址:北京市朝阳区大屯路15号(100101)

英文版个人网页:http://english.ibp.cas.cn/faculty/index_18316.html?json=http://www.ibp.cas.cn/sourcedb_ibp_cas/cn/ibpexport/EN_xsszmA_G/202005/t20200519_5583015.json

课题组网站:http://www.ibp.cas.cn/ggxLab/

简       历:

  1988        毕业于北京大学生物系生物化学专业,获理学士学位

  1995        毕业于美国哥伦比亚大学生化系,获博士学位

  1995 - 1999 美国哥伦比亚大学生化系,Howard Hughes Medical Institute 博士后

  1999 - 2001 美国哥伦比亚大学生化系,Associate Research Scientist 

  2001 - 至今 现为《中国病毒学》和《病毒学报》编委,BMC Microbiology,Associate Editor

获奖及荣誉:

 

社会任职:

 

研究方向:

  病毒感染严重威胁人类健康,对病毒复制机理的了解是开发有效治疗策略的前提和基础。与病毒长期共存过程中,宿主进化产生了多种机制限制病毒的复制;病毒相应地也进化出多种应对宿主排斥的机制。宿主与病毒相互作用是一个精彩的博弈过程。本课题组一直致力于新的宿主抗病毒因子的克隆和机制分析,并以此为基础揭示诸多具有普遍意义的生物学规律。

  在前期的工作中,我们克隆到多个HIV复制相关的宿主蛋白及LncRNA。其中,宿主蛋白ZAP特异性结合病毒mRNA,抑制其翻译起始并招募细胞内mRNA降解机器降解病毒RNA,从而抑制HIV等病毒的复制;宿主蛋白RVB2抑制HIV Gag蛋白表达,而HIV利用了RVB2对Gag表达的调控来优化有效病毒颗粒的产生;宿主蛋白Shiftless通过抑制HIV的 -1位核糖体移码(-1PRF)效率来影响病毒复制。代表性成果发表在《Science》、《Cell》、《Cell Host & Microbe》、《EMBO J》、《Proc Natl Acad Sci USA》等国际学术期刊。

  目前工作方向包括:鉴定新的与HIV、新冠病毒等病毒互作的宿主因子,并解析其作用机制;以Shiftless 为工具鉴定新的发生-1PRF的基因,深入解析-1PRF的生物学意义。

承担项目情况:

 

代表论著:

  1. Luo, X., Wang, X., Gao, Y., Zhu, J., Liu, S., Gao, G.*, Gao, P.*. (2020) Molecular Mechanism of RNA Recognition by Zinc-Finger Antiviral Protein. Cell Rep 30, 46-52 e44

  2. Wang, X., Xuan, Y., Han, Y., Ding, X.,Ye, K., Yang, F., Gao, P., Goff, SP., Gao, G.(2019) Regulation of HIV-1 Gag-Pol Expression by Shiftless, an Inhibitor of Programmed -1 Ribosomal Frameshifting.Cell 176(3): 625-635.

  3. Luo, X., Yang, W., Gao, G. (2018) SUN1 regulates HIV-1 nuclear import in a manner dependent on the interaction between the viral capsid and cellular cyclophilin A. J Virol 92(13). pii: e00229-18.

  4. Zhang, X., Yang, W., Wang, X., Zhang, X., Tian, H., Deng, H., Zhan, L., Gao G.(2018) Identification of new type I interferon-stimulated genes and investigation of their involvement in IFN-β activation. Protein Cell 9(9):799-807.

  5. Chen S, Gao G*. (2017) MicroRNAs recruit eIF4E2 to repress translation of target mRNAs. Protein & Cell 8(10), 750-761.

  6. Zheng X., Wang X., Tu F, Wang Q., Fan Z, Gao G*. (2017) TRIM25 Is Required for the Antiviral Activity of Zinc Finger Antiviral Protein. J Virol 91(9). pii: e00088-17.

  7. Tang Q, Wang X, Gao G*. (2016) ZAPS inhibits influenza A viral protein expression and is antagonized by the virus encoded NS1. J Virol. Nov 2. pii: JVI.01909-16.

  8. Wang X, Li M, Zhao J, Li S, MacDonald M, Rice C, Gao X, Gao G*. (2016) Sindbis virus can exploit a host antiviral protein to evade immune surveillance. J Virol 90(22): p10247-10258.

  9. Wang Q, Zhang X, Han Y, Wang X*, Gao G*. (2016) M2BP inhibits HIV-1 virion production in a vimentin filamentsdependent manner. Scientific Reports. Sep 8;6:32736.

  10. Tao X, Gao G*. (2015) Tristetraprolin Recruits Eukaryotic Initiation Factor 4E2 To Repress Translation of AU-Rich Element-Containing mRNAs. Mol Cell Biol. Nov 15;35(22):3921-32.

  11. Mu X, Fu Y, Zhu Y, Wang X, Xuan Y, Shang H, Goff SP, Gao G*. (2015) HIV-1 exploits RuvB-like 2 to balance viral protein expression. Cell Host & Microbe. Aug 12;18(2):233-42.

  12. Mu X, Li W, Wang X, Gao G*. (2013) YB-1 stabilizes HIV-1 genomic RNA and enhances viral production. Protein & Cell. Aug;4 (8):591-7

  13. Xuan Y, Gong D, Qi J, Han C, Deng H, Gao G*. (2013) ZAP inhibits murine gammaherpesvirus-68 ORF64 expression and is antagonized by RTA, J Virol. 87 (5): 2735-43.

  14. Zhu Y, Wang X, Goff SP, Gao G*. (2012) Translational repression precedes and is required for ZAP-mediated mRNA decay. EMBO J. 31 (21):4236-46.

  15. Li W, Wang X, Gao G*. (2012) Expression of YB-1 enhances production of murine leukemia virus vectors by stabilizing genomic viral RNA. Protein & Cell. Dec;3(12):943-9.

  16. Xuan Y, Liu L, Shen S, Deng H, Gao G*. (2012) Zinc-finger antiviral protein inhibits murine gammaherpesvirus-68 M2 expression and regulates viral latency in cultured cells. J Virol. 86 (22):12431-4.

  17. Wang, X., Tu, F., Zhu, Y., and Gao G*. (2012) Zinc-finger antiviral protein inhibits XMRV infection. PLoS One 7, e39159

  18. Sun L, Lv F, Guo X, Gao G*. (2012) Glycogen synthase kinase 3β (GSK3β) modulates antiviral activity of zinc-finger antiviral protein (ZAP). J Biol Chem. 287 (27): 22882-8.

  19. Chen S, Xu Y, Zhang K, Wang X, Sun J, Gao G*, Liu Y*. (2012) Structure of N-terminal domain of ZAP indicates how a zinc-finger protein recognizes complex RNA. Nat Struct Mol Biol. 19 (4): 430-5.

  20. Zhu Y, Chen G, Lv F, Wang X, Ji X, Xu Y, Sun J, Wu L, Zheng Y, Gao G*. (2011) Zinc-finger antiviral protein inhibits HIV-1 infection by selectively targeting multiply spliced viral mRNAs for degradation. Proc Natl Acad Sci USA. Sep 20;108 (38):15834-9.

  21. Ding J, Su L, Gao G*. (2011) Hrs inhibits citron kinase-mediated HIV-1 budding via its FYVE domain. Protein & Cell. Jun;2 (6):470-6.

  22. Mai Y, Gao G*. (2010) Expression of IMP1 Enhances Production of Murine Leukemia Virus Vector by Facilitating Viral Genomic RNA Packaging. PLoS ONE. Dec 29; 5 (12):e15881.

  23. Ye P, Liu S, Zhu Y, Chen G, Gao G*. (2010) DEXH-Box Protein DHX30 is required for optimal function of the zinc-finger antiviral protein. Protein & Cell. Vol.1 (10),956-964.

  24. Huang Z, Wang X, Gao G*. (2010) Analyses of SELEX-derived ZAP-binding RNA aptamers suggest that the binding specificity is determined by both structure and sequence of the RNA. Protein & Cell. Vol.1(8), 752-759.

  25. Wang X, Lv F, Gao G*. (2010) Mutagenesis analysis of the zinc-finger antiviral protein. Retrovirology. Mar 13;7:19.

  26. Xu J, Liu S, Xu Y, Tian B, Gao G*. (2009) Identification of the nonstructural protein 4B of hepatitis C virus as a factor that inhibits the antiviral activity of interferon-alpha. Virus Research. 141(1): 55–62.

  27. Zhu Y, Gao G*. (2008) ZAP-mediated mRNA degradation.  RNA Biology 5 (2): 65-7 (Invited minireview)

  28. Chen G, Guo X, Lv F, Gao G*. (2008) p72 DEAD box RNA helicase is required for optimal function of the Zinc-finger antiviral protein. Proc Natl Acad Sci USA. 105 (11): 4352-7.

  29. Guo X., Ma J., Sun J., and Gao G*. (2007) The Zinc-finger Antiviral Protein Recruits the RNA Processing Exosome to Degrade Target RNAs. Proc Natl Acad Sci USA. Vol. 104 (1): 151-6

  30. Duan J, Ji X, et al, Gao G*, Yan X* (2006) A human neutralizing antibody against a conformational epitope shared by oligomeric S1 protein. Antiviral Therapy 11(1): 117-23

  31. Liu S, Goff SP and Gao G* (2006) Gln84 of Moloney murine leukemia virus reverse transcriptase regulates the incorporation rates of ribonucleotides and deoxyribonucleotides. FEBS Letters 580: 1497-1501.

  32. Guo X, Carroll JW, Macdonald MR, Goff SP, Gao G*. (2004) The zinc finger antiviral protein directly binds to specific viral mRNAs through the CCCH zinc finger motifs. J Virol. Dec;78(23):12781-7.

  33. Liu L, Chen G, Ji X, Gao G* (2004). ZAP is a CRM1-dependent nucleocytoplasmic shuttling protein. Biochem Biophys Res Commun. Aug 27;321(3):517-23.

  34. Gao G, Goff SP (2004) Isolation of suppressor genes that restore retrovirus susceptibility to a virus-resistant cell line. Retrovirology. Sep 28;1 (1):30.

  35. Gao, G.,Guo,X and Goff, S.P. (2002). Inhibition of Retroviral RNA Production by ZAP, a CCCH-type Antiviral Protein. Science 297:1703-1706.

  36. 王俊,王延轶,王盛典,田志刚,刘利新,刘昱,杨艳,李姝,李颖,陈宇,陈永艳,陈桂芳,郑世军,钟波,郭德银,高光侠,康曦,舒红兵,抗病毒天然免疫(内源性免疫:宿主限制因子),科学出版社,39万字,2009

 

(资料来源:高光侠研究员,2020-11-16)