雷曉光

特聘研究員，博士生導師；化學遺傳學，有機合成化學

E-mail：xglei@pku.edu.cn
實驗室主頁: http:/leigroup

教育和研究背景：

2001年本科畢業于beat365官方网站，2006年獲得美國波士頓大學理學博士學位，2006-2008年在美國哥倫比亞大學和斯隆-凱特林癌症研究中心從事生物有機化學博士後研究；2008年底全職回國，曾任天津大學藥物科學與技術學院教授，北京生命科學研究所高級研究員，化學中心主任；2014年初全職加入beat365官方网站化學生物學系，任特聘研究員，博士生導師，同時任beat365合成與功能生物分子中心，北大-清華生命科學聯合中心研究員；中國化學會、藥學會，美國化學會，中美化學教授協會，國際化學生物學會會員；國家中青年科技創新領軍人才（2013），優秀青年基金（2012）獲得者；曾獲得國際化學生物學會首屆青年化學生物學家獎（2013），中國化學會青年化學獎（2013），中國藥學會“施維雅青年藥物化學獎”（2013），Thieme Chemistry Journal Award （2013），和藥明康德生命化學科研獎（2010）等多項學術榮譽。

研究方向：

小分子影響了許多重要的生物過程，因此它們可以被認為是生物中心法則的另一個重要的組成成分。具有生物活性的小分子可以是通過自然進化選擇的天然産物，也可以是通過有機合成制造的藥物分子和化學探針。我們課題組緻力于應用新穎的活性小分子和化學手段去系統深入地研究重要生命過程，闡明生物信号傳導通路中新的分子作用機制，去驗證全新的藥物靶點從而幫助解決重大醫學難題。

具體研究内容包括以下四個方面：

1）利用化學遺傳學手段研究與人類重大疾病（如：癌症，感染性疾病，神經退行性疾病等）相關的生物通路分子作用機制和調控方法；

2）運用活性天然産物發現新的生物靶點和闡明新的生物作用機制；

3）開發新一代高效的生物相容反應，并且将其應用在生物分子标記，追蹤等化學生物學研究中；

4）尋找和發現新的藥物靶點，利用藥物化學手段設計并且合成相關小分子進行創新藥物的研究。

代表性論文：

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”)