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雷晓光

 

 

特聘研究员,博士生导师;化学遗传学,有机合成化学

 

E-mailxglei@pku.edu.cn
实验室主页:
http://www.chem.pku.edu.cn/leigroup

 

教育和研究背景:


2001年本科毕业于北京大学化学与分子工程学院,2006年获得美国波士顿大学理学博士学位,2006-2008年在美国哥伦比亚大学和斯隆-凯特林癌症研究中心从事生物有机化学博士后研究;2008年底全职回国,曾任天津大学药物科学与技术学院教授,北京生命科学研究所高级研究员,化学中心主任;2014年初全职加入北京大学化学与分子工程学院化学生物学系,任特聘研究员,博士生导师,同时任北京大学合成与功能生物分子中心,北大-清华生命科学联合中心研究员中国化学会、药学会,美国化学会,中美化学教授协会,国际化学生物学会会员;国家中青年科技创新领军人才(2013),优秀青年基金(2012)获得者;曾获得国际化学生物学会首届青年化学生物学家奖(2013),中国化学会青年化学奖(2013),中国药学会“施维雅青年药物化学奖”(2013Thieme Chemistry Journal Award 2013),和药明康德生命化学科研奖(2010等多项学术荣誉。

 

研究方向:


小分子影响了许多重要的生物过程,因此它们可以被认为是生物中心法则的另一个重要的组成成分。具有生物活性的小分子可以是通过自然进化选择的天然产物,也可以是通过有机合成制造的药物分子和化学探针。我们课题组致力于应用新颖的活性小分子和化学手段去系统深入地研究重要生命过程,阐明生物信号传导通路中新的分子作用机制,去验证全新的药物靶点从而帮助解决重大医学难题。

具体研究内容包括以下四个方面:

1)利用化学遗传学手段研究与人类重大疾病(如:癌症,感染性疾病,神经退行性疾病等)相关的生物通路分子作用机制和调控方法;

2)运用活性天然产物发现新的生物靶点和阐明新的生物作用机制;

3)开发新一代高效的生物相容反应,并且将其应用在生物分子标记,追踪等化学生物学研究中;

4)寻找和发现新的药物靶点,利用药物化学手段设计并且合成相关小分子进行创新药物的研究。

 

代表性论文:


1. Li, Q.; Dong, T.; Liu, X.; Lei, X.* “A Bioorthogonal Ligation Enabled by Click Cycloaddition of o-Quinolinone Quinone Methide and Vinyl Thioether” J. Am. Chem. Soc. 2013, 135, 4996-4999. (News story describing this work was highlighted in Chem. & Eng. News 2013, 14, 37).

2. Li, T.; Chen, J.; Li, X.; Ding, X.; Wu, Y.; Zhao, L.; Chen, S.; Lei, X.*; Dong, M.* “Absolute Quantification of a Steroid Hormone that Regulates Development in Caenorhabditis elegans” Anal. Chem. 2013, 85, 9281-9287.

3. Li, C.; Dong, T.; Dian, L.; Zhang, W.; Lei, X.* “Biomimetic Syntheses and Structural Elucidation of the Apoptosis-Inducing Sesquiterpenoid Trimers: (-)-Ainsliatrimers A and B” Chem. Sci. 2013, 4, 1163-1167.

4. Wang, G.;* Wang, X.; Yu, H.; Wei, S.; Williams, N.; Holmes, D. L.; Halfmann, R.; Naidoo, J.; Wang, L.; Li, L.; Chen, S.; Harran, P.; Lei, X.*; Wang, X.* “Small Molecule Activation of the TRAIL Receptor DR5 in Human Cancer Cells” Nat. Chem. Biol. 2013, 2, 84-90. (News stories describing this work were highlighted in Chem. & Eng. News 2013, 2, 37; Nature Asia 2012, December 24).

5. Li, H.; Wang, X.; Hong, B.; Lei, X.* “Collective Synthesis of Lycopodium Alkaloids and Tautomer Locking Strategy for the Total Synthesis of (-)-Lycojapodine A” J. Org. Chem. 2013, 78, 800-821. (Featured and Cover Article).

6. Li, C.; Dian, L.; Zhang, W.; Lei, X.* “Biomimetic Syntheses of (-)-Gochnatiolides A-C and (-)-Ainsliadimer B” J. Am. Chem. Soc. 2012, 134, 12414-12417.

7. Sun, L.; Wang, H.; Wang, Z.; He, S.; Chen, S.; Liao, D.; Wang, L.; Yan, J.; Liu, W.; Lei, X.*; Wang, X.* “Mixed Lineage Kinase Domain-like Protein Mediates Necrosis Signaling Downstream of  RIP3 Kinase” Cell 2012, 148, 213-227. (News stories describing this work were highlighted in Chem. & Eng. News 2012, 5, 40; Nature China 2012, February 1; Asian Scientist 2012, January31; and Nature Reviews Molecular Cell Biology, 2012, Feb. 8).

8. Li, H.; Wang, X.; Lei, X.* “Total Syntheses of Lycopodium Alkaloids (+)-Fawcettimine, (+)-Fawcettidine and (-)-8-Deoxyserratinine” Angew. Chem. Int. Ed. 2012, 51, 491-495; Angew. Chem. 2012, 124, 506-510.

9. Liao, D.; Li, H.; Lei, X.* “Efficient Generation of ortho-Quinone Methide: Application to the Biomimetic Syntheses of (±)-Schefflone and Tocopherol Trimers” Org. Lett. 2012, 14, 18-21.

10. Li, C.; Tu, S.; Wen, S.; Li, S.; Chang, J.; Shao, F.; Lei, X.* “Total Synthesis of the G2/M DNA Damage Checkpoint Inhibitor Psilostachyin C” J. Org. Chem. 2011, 76, 3566-3570.

11. Chou, T.; Dong, H.; Zhang, X.; Lei, X.; Hartung, J.; Zhang, Y.; Lee, H. L.; Wilson, R. M.; Danishefsky, S. J. * “Multifaceted Cytoprotection by Synthetic Polyacetylenes Inspired by the Ginseng-derived Natural Product Panaxytriol” Proc. Natl. Acad. Sci. 2011, 108, 14336-14341.

12. Li, C.; Yu, X.; Lei, X.* “A Biomimetic Total Synthesis of (+)-Ainsliadimer A” Org. Lett. 2010, 12, 4284-4287.

13. Gong, Y.; Wang, X.; Wang, J.; Yang, Z.; Li, S.; Yang, J.; Liu, L.; Lei, X.*; Shao, F. * “Chemical Probing Reveals Insights into the Signaling Mechanism of Inflammasome Activation” Cell Res. 2010, 20, 1289-1305.

14. Han,Z.; Niu, T.; Chang, J.; Lei, X.; Zhao, M.; Wang, Q.; Cheng, W.; Wang, J.; Feng, Y.; Chai, J.* “Crystal structure of the FTO protein reveals basis for its substrate specificity” Nature 2010, 464, 1205-1209.

15. Lei, X.; Danishefsky, S. J.* “Efficient Synthesis of a Novel Resorcyclide as Anticancer Agent Based on Hsp90 Inhibition” Adv. Synth. Catal. 2008, 350, 1677-1681。

16. Lei, X.; Porco, J. A., Jr.* “Total Synthesis of the Diazobenzofluorene Antibiotic (-)-Kinamycin C.” J. Am. Chem. Soc. 2006, 128, 14790-14791. (News story describing this work was highlighted in Chem. & Eng. News 2006, 45, 9)

17. Porco, J. A., Jr.*; Su, S.; Lei, X.; Bardhan, S.; Rychnovsky, S. D. “Total Synthesis and Structure Assignment of (+)-Hexacyclinol” Angew. Chem. Int. Ed. 2006, 45, 5790-5792; Angew. Chem. 2006, 118, 5922-5924. (News stories describing this work were reported in Chem. & Eng. News 2006, 31, 11 and Nature 2006, 442, 492-493)

18. Lei, X.; Zaarur, N.; Sherman, M. Y.; Porco, J. A., Jr.* “Stereocontrolled Synthesis of a Complex Chemical Library via Elaboration of Angular Epoxyquinol Scaffolds.” J. Org. Chem. 2005, 70, 6474-6483.

19. Lei, X.; Porco, J. A., Jr.* “Synthesis of a Polymer-Supported Anthracene and Its Application as a Dienophile Scavenger.” Org. Lett. 2004, 6, 795-798.

20. Lei, X.; Johnson, R. P.; Porco, J. A., Jr.* “Total Synthesis of the Ubiquitin-Activating Enzyme Inhibitor (+)-Panepophenanthrin.” Angew. Chem. Int. Ed. 2003, 42, 3913-3917; Angew. Chem. 2003, 115, 4043-4047. (This publication was highlighted as a “Hot Paper”)


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