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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/faculty/index_18316.html?json=http://www.ibp.cas.cn/sourcedb_ibp_cas/cn/ibpexport/EN_xsszmA_G/202005/t20200519_5583013.json

 

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:

  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) [注:因全职回国工作,已放弃该经费奖励。]

  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、结构生物学和细胞生物学等手段,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生物学工具的开发提供依据和思路。近年来课题组主要聚焦在“宿主对病原DNA的免疫识别”和“病原对宿主的干预修饰”两个研究方向。

  

承担项目情况:

 

代表论著:

  1. Lama L#, Adura C#, Xie W#, Tomita D, Kamei T, Kuryavyi V, Gogakos T, Steinberg J, Miller M, Ramos-Espiritu L, Asano Y, Hashizume S, Aida J, Imaeda T, Okamoto R, Jennings A, Michino M, Kuroita T, Stamford A, Gao P, Meinke P*, Glickman F*, Patel D*, Tuschl T* (2019). Development of human cGAS-specific small molecule inhibitors for repression of dsDNA-triggered interferon expression, Nat Commun. 10:2261.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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:

  10. Ren A#, Vu?urovi? N#, Gebetsberger J, Gao P, Juen M, Kreutz C, Micura R*, and Patel DJ* (2016). Pistol ribozyme adopts a pseudoknot fold facilitating site-specific in-line cleavage. Nat Chem Bio. 12(9):702-8.

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

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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 ? 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.

  2. 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,2019-10-17)