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创新研究群体项目获得者

高璞博士研究员博士生导师

国家“杰出青年基金”获得者
中科院生物物理所，生物大分子重点实验室，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/sourcedb/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：

2024年陈嘉庚青年科学奖

2023年谈家桢生命科学创新奖

2023年中国科学院青年科学家奖

2023年国家自然基金委杰出青年基金

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：

1. Huang J^#, Zhang X^#, Nie X, Zhang X, Wang Y, Huang L, Geng X, Li D, Zhang L*, Gao G*, Gao P* (2024). Assembly and activation of EBV latent membrane protein 1. Cell. doi: 10.1016/j.cell.2024.06.021.

2. Ma S^#*, Sandhoff R^#, Luo X^#, Shang F^#, Shi Q, Li Z, Wu J, Ming Y, Schwarz F, Madi A, Weisshaar N, Mieg A, Hering M, Zettl F, Yan X, Mohr K, Bosch NT, Li Z, Poschet G, Rodewald HR, Papavasiliou N, Wang X*, Gao P*, Cui G* (2024). Serine enrichment in tumors promotes regulatory T cell accumulation through sphinganine-mediated regulation of c-Fos. Sci Immunol. 19;9(94):eadg8817.

3. Li Q*, Gao P* (2024). Phase separation in cGAS-STING signaling. Front Med. 17(5):855-866.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.

10. 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.

11. 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.

12. 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.

13. 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.

14. 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.

15. 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.

16. 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.

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

18. 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.

19. 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.

20. 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.

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

22. 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.

23. 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.

24. 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.

25. 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.

26. 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.

27. 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.

28. 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，2024-07-30）