高璞

中国科学院生物物理研究所

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  • 高璞
  • 研究员

高璞 博士 研究员 博士生导师

国家“青年千人计划”,国家“优秀青年基金”

中国科学院生物物理所,中国科学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(E-mail):gaopu(AT)ibp.ac.cn

电话(Tel):010-64887199

邮政编码:100101

英文版个人网页

简历 & 研究组工作摘要

2016-今 中国科学院生物物理研究所(研究员)

2011-2016 美国纪念斯隆-凯特琳癌症中心(博士后、研究助理)

2005-2011 中国科学院生物物理研究所(博士)

2001-2005 山东大学(学士)

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。

代表性奖励

2019 第四届中源协和生命医学创新突破奖

2019 国家自然基金委优秀青年基金

2018 中国晶体学会第一届青年科技奖

2016 国家青年千人计划

2016 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 Irvington Postdoctoral Fellowship Award(美国癌症研究所)

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

2009 David Blow Visiting Scholarship(英国CCP4协会)

代表性论文(* Corresponding Authors, # First Authors)

加入生物物理所之后:

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网页更新