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中国科学院感染与免疫重点实验室

高璞博士研究员博士生导师

国家“优秀青年基金”获得者 中科院生物物理所，中科院感染与免疫重点实验室，研究组长

研究方向：宿主-病原相互作用的分子机制

电子邮件：gaopu@ibp.ac.cn

电话：010-64887199

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/en_sourcedb_ibp/rck/EN_xsszmA_G/202005/t20200519_341412.html

简历：

　　2001 - 2005 山东大学，学士

　　2005 - 2011 中国科学院生物物理研究所，博士

　　2011 - 2016 美国纪念斯隆-凯特琳癌症中心，博士后、研究助理

　　2016 - 至今中国科学院生物物理研究所，研究员

获奖及荣誉：

　　2021年 20年中免疫学20项标志性进展（Nature Review Immunology）

　　2020年中国科学院引才计划终期评估优秀

　　2019年第四届中源协和生命医学创新突破奖

　　2019年国家自然基金委优秀青年基金

　　2018年中国晶体学会第一届青年科技奖

　　2016年 NIH Pathway to Independence Award (K99/R00)（美国国立卫生研究院）

　　2014年 Irvington Postdoctoral Fellowship Award（美国癌症研究所）

　　2013年 Postdoctoral Research Award（美国纪念斯隆-凯特琳癌症中心）

　　2009年 David Blow Visiting Scholarship（英国CCP4协会）

社会任职：

研究方向：

　　本课题组的研究领域为宿主-病原相互作用，综合运用生物化学、结构生物学、细胞生物学和动物模型等手段，致力于揭示宿主-病原互作的分子机制，为相关疾病的治疗和新型工具的开发提供依据和思路。近年来课题组主要聚焦“宿主对异常核酸信号的免疫应答及调控”这一研究方向。

承担项目情况：

代表论著：

加入生物物理所之后：

1. Gao Y, Luo X, Li P, Li Z, Ye F, Liu S,Gao P*(2023). Molecular basis of RADAR anti-phage supramolecular assemblies.Cell. 186(5):999-1012.e20.

2. Zhang Q^#, Zhang X^#, Zhu Y^#, Sun P^#, Zhang L, Ma J, Zhang Y, Zeng L, Nie X, Gao Y, Li Z, Liu S, Lou J, Gao A*, Zhang L*,Gao P*(2022). Recognition of cyclic dinucleotides and folates by human SLC19A1.Nature. 612(7938):170-176.

3. Zhu J, Gao Y, Wang Y, Zhan Q, Feng H, Luo X, Li P, Liu S, Hou H*,Gao P*(2022) Molecular insights into DNA recognition and methylation by non-canonical type I restriction-modification systems.Nat Commun. 13(1): 6391.

4. Shen C^#, Li R^#, Negro R, Cheng J, Vora SM, Fu TM, Wang A, He K, Andreeva L,Gao P, Tian Z, Flavell RA, Zhu S*, Wu H* (2021). Phase separation drives RNA virus-induced activation of the NLRP6 inflammasome.Cell. 184(23):5759-5774.e20.

5. Xu G^#, Liu C^#, Zhou S^#, Li Q, Feng Y, Sun P, Feng H, Gao Y, Zhu J, Luo X, Zhan Q, Liu S, Zhu S, Deng H*, Li D*,Gao P*(2021). Viral tegument proteins restrict cGAS-DNA phase separation to mediate immune evasion.Mol Cell. 81(13):2823-2837.e9.

6. Feng H^#, Tian H^#, Wang Y, Zhang Q, Lin N, Liu S, Yu Y, Deng H*,Gao P*(2020). Molecular mechanism underlying selective inhibition of mRNA nuclear export by herpesvirus protein ORF10,PNAS. 117(43):26719-26727.

7. Wang Y^#, Zhan Q^#, Wang X, Li P, Liu S, Gao G,Gao P*(2020). Insights into catalysis and regulation of non-canonical ubiquitination and deubiquitination by bacterial deamidase effectors,Nat Commun. 11(1):2751.

8. Gao Y^#, Cao D^#, Zhu J, Feng H, Luo X, Liu S, Yan XX, Zhang X*,Gao P*(2020). Structural insights into assembly, operation and inhibition of a type I restriction-modification system,Nat Microbiol. 5(9):1107-1118.

9. 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 Reports. 30(1):46-52.e4.

10. Zhu Y^#, Gao A^#, Zhan Q, Wang Y, Feng H, Liu S, Gao G, Serganov A*,Gao P*(2019). Diverse mechanisms of CRISPR-Cas9 inhibition by type IIC anti-CRISPR proteins.Mol Cell.74(4):296-309.

11. 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.

12. Wang Y, Shi M, Feng H, Zhu Y, Liu S, Gao A*,Gao P*(2018). Structural insights into non-canonical ubiquitination catalyzed by SidE.Cell. 173(5): 1231-1243.

13. Liu YP, Tang Q, Zhang JZ, Tian LF,Gao P*, and Yan XX* (2017). Structural basis underlying complex assembly and conformational transition of the type I R-M system.PNAS. 114(42): 11151-6.

14. Wang Y^#, Feng H^#, Zhu Y, andGao P*(2017). Structural insights into glutathione-mediated activation of the master regulator PrfA in Listeria monocytogenes.Protein Cell. 8(4):308-12.

15. Vincent J^#, Adura C^#,Gao P^#, Luz A, Lama L, Asano Y, Okamoto R, Imaeda T, Aida J, Rothamel K, Gogakos T, Steinberg J, Reasoner S, Aso K, Tuschl T, Patel DJ*, Glickman JF*, and Ascano M* (2017). Small molecule inhibition of cGAS reduces interferon expression in primary macrophages from autoimmune mice.Nat Commun. 8(1): 750.

16. Yang H,Gao P, Rajashankar KR, and Patel DJ*. (2016). PAM-Dependent Target DNA Recognition and Cleavage by C2c1 CRISPR-Cas Endonuclease.Cell. 167(7):1814-28.

17.Gao P*, Yang H, Rajashankar KR, Huang Z, and Patel DJ* (2016). Type V CRISPR-Cas Cpf1 endonuclease employs a unique mechanism for crRNA-mediated target DNA recognition.Cell Research. 26(8):901-13.

加入生物物理所之前：

18.Gao P, and Patel DJ (2015). V-cGAPs: Attenuators of 3'3'-cGAMP signaling.Cell Research. 25(5): 529-30.

19.Gao P^#, Zillinger T^#, Wang W, Ascano M, Dai P, Hartmann G, Tuschl T, Deng L, Barchet W*, and Patel DJ* (2014). Binding-Pocket and Lid-Region Substitutions Render Human STING Sensitive to the Species-Specific Drug DMXAA.Cell Reports. 8(6): 1668-76.

20.Gao P^#, Ascano M^#, Zillinger T^#, Wang W, Dai P, Serganov AA, Gaffney BL, Shuman S, Jones RA, Deng L, Hartmann G, Barchet W*, Tuschl T*, and Patel DJ* (2013). Structure-Function Analysis of STING Activation by c[G(2',5')pA(3',5')p] and Targeting by Antiviral DMXAA.Cell. 154(4):748-62.

21.Gao P^#, Ascano M^#, Wu Y, Barchet W, Gaffney BL, Zillinger T, Serganov AA, Liu Y, Jones RA, Hartmann G, Tuschl T*, and Patel DJ* (2013). Cyclic [G(2',5')pA(3',5')p] is the metazoan second messenger produced by DNA-activated cyclic GMP-AMP synthase.Cell. 153(5):1094-107.

22. Oh YS,Gao P, Lee KW, Ceglia I, Seo JS, Zhang X, Ahn JH, Chait BT, Patel DJ, Kim Y*, and Greengard P* (2013). SMARCA3, a chromation-remodeling factor, is required for p11-dependent antidepressant action.Cell. 152(4): 831-43.

23. Tang Q,Gao P, Liu YP, Liu S, Gao A, An XM, Yan XX*, and Liang DC* (2012). RecOR complex including RecR N-N dimer and RecO monomer displays a high affinity for ssDNA.Nucleic Acids Res. 40(21): 11115-25.

24.Gao P, Tang Q, An XM, Yan XX*, and Liang DC* (2011). Structure of HsdS subunit from Thermoanaerobacter tengcongensis sheds lights on mechanism of dynamic opening and closing of type I methyltransferase.PLoS One. 6(3): e17346.

25. Shi L^#,Gao P^#, Yan XX, and Liang DC* (2009). Crystal structure of a putative methylmalonyl-coenzyme A epimerase from Thermoanaerobacter tengcongensis at 2.0 angstrom resolution.Proteins. 77(4), 994-9.

国际专利：

1. Compositions and methods for altering second messenger signaling. Patent No.: US10131686B2.

2. Compositions and methods for altering second messenger signaling. Patent No.: US9840533B2.

3. STING crystals and modulators. Patent No.: US10176292B2.

目前这3项专利都已成功商业转化，所开发的药物已经在美国进入临床实验。

（资料来源：高璞研究员，2023-04-07）