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雷晓光

教授,博士生导师

化学生物学,天然产物合成,药物化学

办公室:化学楼 A-509
实验室:化学楼 A-504, A-606
电话: +86-10-62760292
Email:xglei@pku.edu.cn
课题组网站:http://www.chem.pku.edu.cn/leigroup

教育背景:

2001-2006 美国波士顿大学 博士(有机合成化学) 导师:John Porco 教授
1997-2001 北京大学 理学学士(化学) 导师:王剑波 教授

工作背景:

2017-现在 北京大学 化学学院 新体制长聘正教授, 博士生导师
2014-现在 北大-清华生命科学联合中心 高级研究员
2014-2017 北京大学 化学学院 特聘研究员with tenure ,博士生导师
2013-2014 北京生命科学研究所 高级研究员
2008-2012 北京生命科学研究所 研究员, 化学中心主任
2008-2013 天津大学 药学院 副教授, 教授
2006-2008 美国哥伦比亚大学 博士后(生物有机化学)    合作导师:Samuel Danishefsky 教授

学术奖励:

北京市“卓越青年科学家”计划,2018
David Ginsburg Award, 2018
中国化学会-巴斯夫青年知识创新奖,2018
Tetrahedron Young Investigator Award in Bioorganic and Medicinal Chemistry, 2017
Swiss Chemical Society Distinguished Lectureship Award, 2017
KAIST School of Molecular Science Lectureship Award, 2017
国家杰出青年科学基金, 2016
Asian Core Program Lectureship Award, 2016
Distinguished Lectureship Award by Chemical Society of Japan (CSJ), 2015
中国化学会-"维善天然产物合成奖",2015
中组部万人计划-青年拔尖人才,2015
Roche Young Investigator Award, 2014
北京市优秀青年人才,2014
科技部中青年科技创新领军人才,2013
中国化学会"青年化学奖",2013
国际化学生物学协会(ICBS)首届"Young Chemical Biologist Award",2013
中国药学会"施维雅青年药物化学奖",2013
Thieme Chemistry Journal Award, 2013
Asian Core Program Lectureship Award, 2012
国家优秀青年科学基金, 2012
教育部新世纪优秀人才, 2010
药明康德生命化学杰出科研奖, 2010
IUPAC Young Chemist Award, 2009
NESACS-JCF/GDCh Exchange Scholarship, 2005
Sugata Ray Memorial Award for Excellence in Research at Boston University, 2005

研究领域:

化学生物学,天然产物合成,合成生物学,创新药物研发

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。我们课题组致力于发展和应用新颖的活性小分子和化学技术去系统深入地研究重要生命过程,阐明与人类重大疾病密切相关的生物信号转导通路中新的分子作用机制,去验证全新的药物靶点,从而帮助解决重大生物医学难题。具体研究内容包括以下五个方面:
  • 利用化学生物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;
  • 开展复杂天然产物合成研究,并且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;
  • 研究复杂天然产物生物合成,揭示新的酶学机制,并且综合运用合成化学与合成生物学手段高效制备天然产物来源的药物分子;
  • 开发新一代高效的生物相容反应,并且利于化学交联结合质谱技术系统研究复杂蛋白质结构和蛋白-蛋白相互作用;
  • 寻找和发现新的药物靶点,利用药物化学手段开发创新型药物。

代表性论文:

  1. Xiao F, Zhang X, Lei X.* “Recent Developments and Applications of Photoconjugation Chemistry”. Chimia 2018, 72, 782-790
  2. Zhu H, Zhang L, Wu Y, Dong B, Guo W, Wang M, Yang L, Fan X, Tang Y, Liu N, Lei X, Wu H.* “T-ALL leukemia stem cell 'stemness' is epigenetically controlled by the master regulator SPI1”. Elife 2018, pii: e38314. DOI: 10.7554/eLife.38314
  3. Ye, Z.; Zhang, X.; Zhu, Y.; Song, T.; Chen, X.; Lei, X.*; Wang, X.* “Chemoproteomic Profiling Reveals Ethacrynic Acid Targets Adenine Nucleotide Translocases to Impair Mitochondrial Function” Mol. Pharm. 2018, 15, 2413-2422
  4. Dong Q, Li X, Wang CZ, Xu S, Yuan G, Shao W, Liu B, Zheng Y, Wang H, Lei X, Zhang Z, Zhu B.* “Roles of the CSE1L-mediated nuclear import pathway in epigenetic silencing” Proc Natl Acad Sci U S A. 2018, 115, E4013-E4022
  5. Ozaki T, Shinde SS, Gao L, Okuizumi R, Liu C, Ogasawara Y, Lei X, Dairi T, Minami A, Oikawa H.* “Enzymatic formation of a skipped methyl-substituted octaprenyl side chain of longestin (KS-505a): Involvement of homo-IPP as a common extender unit” Angew. Chem. Int. Ed. 2018, 57, 6629-6632
  6. Yue, Z.; Xiao, X.; Wu, J.; Zhou, X.; Liu, W.; Liu, Y.; Li, H.; Chen, G.; Wu, Y.*; Lei, X.* “ent-Jungermannenone C Triggers Reactive Oxygen Species-Dependent Cell Differentiation in Leukemia Cells” J. Nat. Prod. 2018, 81, 298-306
  7. Zhang, X.; Wang, J.; Tan, D.; Li, Q.; Li, M.; Gong, Z.; Tang, C.; Liu, Z.; Dong, W.*; Lei, X.* “Carboxylate-Selective Chemical Cross-Linkers for Mass Spectrometric Analysis of Protein Structures” Anal. Chem. 2018, 90, 1195-1201
  8. Li, H.; Lei, X.* “Fawcettimine-Type Lycopodium Alkaloids as a Driving Force for Discoveries in Organic Synthesis” Chem. Rec. 2018, 18, 543-554
  9. Zhang, J.; Wang, S.; Bai, Y.; Guo, Q.; Zhou, J.; Lei, X.* “Total Syntheses of Natural Metallophores Staphylopine and Aspergillomarasmine A” J. Org. Chem. 2017, 82, 13643-13648.
  10. Zhang, J.; Wang, S.; Wei, Q.; Guo, Q.; Bai, Y.; Yang, S.; Song, F.; Zhang, L.; Lei, X.* “Synthesis and biological evaluation of Aspergillomarasmine A derivatives as novel NDM-1 inhibitor to overcome antibiotics resistance.” Bioorg. Med. Chem. 2017, 25, 5133-5141.
  11. Han, X.; Yang, Y.; Wu, Y.; Liu, X.; Lei, X.*; Guo, Y.* “A bioassay-guided fractionation system to identify endogenous small molecules that activate plasma membrane H+-ATPase activity in Arabidopsis.” J. Exp. Bot. 2017, 68, 2951-2962.
  12. Hong, B.; Hu, D.; Wu, J.; Zhang, J.; Li, H.; Pan, Y.; Lei, X.* “Divergent Total Syntheses of (-)-Huperzine Q, (+)-Lycopladine B, (+)-Lycopladine C and (-)-epi-Lycopladine D” Chem. Asian J. 2017, 12, 1557-1567. (VIP paper)
  13. Zhuang, S.; Li, Q.; Cai, L.; Wang, C.*; Lei, X.* “Chemoproteomic Profiling of Bile Acid Interacting Proteins” ACS Cent. Sci. 2017, 3, 501-509.
  14. Jones, A.; Zhang, X.; Lei, X.* “Covalent Probe Finds Carboxylic Acid” Cell Chem. Biol. 2017, 24, 537-538.
  15. Ren, Y.; Su, Y.; Su, L.; He, S.; Meng, L.; Liao, D.; Liu, X.; Ma, Y.; Liu, C.; Li, S.; Ruan, H.; Lei, X.; Wang, X.*; Zhang, Z.* “Discovery of a Highly Potent, Selective, and Metabolically Stable Inhibitor of Receptor-Interacting Protein 1 (RIP1) for the Treatment of Systemic Inflammatory Response Syndrome” J. Med. Chem. 2017, 60, 972-986.
  16. Siridechakorn, I.; Yue, Z.; Mittraphab, Y.; Lei, X.; Pudhom, K.* “Identification of spirobisnaphthalene derivatives with anti-tumor activities from the endophytic fungus Rhytidhysteron rufulum AS21B” Bioorg. Med. Chem. 2017, 25, 2878-2882.
  17. Liu, X.; Dong, T.; Zhou, Y.; Huang, N.; Lei, X.* “Exploring the Binding Proteins of Glycolipids with Bifunctional Chemical Probes” Angew. Chem. Int. Ed. 2016, 55, 14330-14334.
  18. Tan, D.; Li, Q.; Zhang, M.; Liu, C.; Ma, C.; Zhang, P.; Ding, Y.; Fan, S.; Tao, L.; Yang, B.; Li, X.; Ma, S.; Liu, J.; Feng, B.; Liu, X.; Wang, H.; He, S.; Gao, N.; Ye, K.; Dong, M.*; Lei, X.* “Trifunctional Cross-Linker for Mapping Protein-Protein Interaction Networks and Comparing Protein Conformational States” eLife 2016; 5:e12509. (News story describing this work was highlighted by Nature Methods 2016, 13, 392-392).
  19. Li, C.; Jones, A.; Lei, X.* “Synthesis and Mode of Action of Oligomeric Sesquiterpene Lactones” Nat. Prod. Rep. 2016, 33, 602-611. (Cover story)
  20. Shang, E.; Zhang, J.; Bai, J.; Wang, Z.; Li, X.; Zhu, B.; Lei, X.* “Syntheses of [1,2,4]triazolo[1,5-a]benzazoles Enabled by the Transition-Metal-Free Oxidative N-N Bond Formation” Chem. Commun. 2016, 52, 7028-7031.
  21. Liao, D.; Yang, S.; Wang, J.; Zhang, J. Hong, B.; Wu, F.; Lei, X.* “Total Synthesis and Structural Reassignment of Aspergillomarasmine A” Angew. Chem. Int. Ed. 2016, 55, 4291-4295.
  22. Liu, W.; Li, H.; Cai, P.; Wang, Z.; Yu, Z-X.; Lei, X.* “Scalable Total Synthesis of Jungermannenones B and C” Angew. Chem. Int. Ed. 2016, 55, 3112-3116. (Highlighted by Synfacts 2016, 12, 0332).
  23. Li, D.; Li, C.; Li, L.; Chen. S.; Wang, L.; Li, Q.; Wang, X.; Lei, X.*; Shen, Z.* “Natural Product Kongensin A is a Non-Canonical HSP90 Inhibitor that Blocks RIP3-dependent Necroptosis” Cell Chem. Biol. 2016, 23, 257-266. (Featured article, and highlighted by Jacobsen et al. Cell Chem. Biol. 2016, 23, 205-207).
  24. Gao, L.; Han, J.; Lei, X.* “Enantioselective Total Syntheses of Kuwanon X, Kuwanon Y and Kuwanol A” Org. Lett. 2016, 18, 360-363.
  25. Yang, S.; Liao, D.; Tian, X.; Lei, X.* “Access to the 2H-tetrahydro-4, 6-dioxo-1, 2-oxazine Ring System from Nitrone via a Tandem Nucleophilic Addition and Transesterification Re-action” Org. Lett. 2016, 18, 376-379.
  26. Dong, T.; Liu, W.; Shen, Z.; Li, L.; Chen, S.; Lei, X.* “Pterisolic Acid B is a Nrf2 Activator by Targeting C171 within Keap1-BTB Domain” Sci. Rep. 2016, 6, 19231.
  27. Ma, K.; Liao, D.; Yang, S.; Li, X.; Lei, X.* “Studies towards the Synthesis of the Functionalized C3-C14 Decalin Framework of Alchivemycin A” Org. Chem. Front. 2016, 3, 251-258.
  28. Li, X.; Han, J.; Jones, A.; Lei, X.* “Chiral Boron Complex-Promoted Asymmetric Diels-Alder Cycloaddition and Its Application in Natural Product Synthesis” J. Org. Chem. 2016, 81, 458-468.
  29. Hong, B.; Li, C.; Wang, Z.; Chen, J.; Li, H.*; Lei, X.* “Enantioselective Total Synthesis of (-)-Incarviatone A” J. Am. Chem. Soc. 2015, 137, 11946-11949. (News story describing this work was highlighted by Chem. & Eng. News 2015, 93, 35 and Synfacts 2015, 11, 1231).
  30. Dong, T.; Liao, D.; Liu, X.; Lei, X.* “Using Small Molecules to Dissect Non-apoptotic Programmed Cell Death” ChemBioChem 2015, 16, 2557-2561.
  31. Ren, R.; Zhou, X.; He, Y.; Ke, M.; Wu, J.; Liu, X.; Yan, C.; Wu, Y.; Gong, X.; Lei, X.; Yan, S. F.; Radhakrishnan, A.; Yan, N.* “Crystal structure of a mycobacterial Insig homolog provides insight into how these sensors monitor sterol levels” Science 2015, 349, 187-191.
  32. Zhang, X.; Dong, T.; Li, Q.; Liu, X.; Li, L.; Chen, S.; Lei, X.* “Second-Generation TQ-Ligation for Cell Organelle Imaging” ACS Chem. Biol. 2015, 10, 1676-1683.
  33. Han, J.; Jones, A.; Lei, X.* “Recent Advances in the Total Synthesis of Prenylflavonoid and Related Diels-Alder Natural Products” Synthesis 2015, 47, 1519-1533.
  34. Dong, T.; Li, C.; Wang, X.; Dian, L.; Zhang, X.; Chen, X.; Li, L.; Cao, R.; Huang, N.; He, S. *; Lei, X.* “Ainsliadimer A selectively inhibits IKKα/β by covalently binding a conserved cysteine” Nature Commun. 2015, 6, 6522. (News story describing this work was highlighted in Chem. & Eng. News 2015, 15, 39).
  35. Liu, W.; Li, X.; Chen, J.; Li, T.; Dong, M.; Lei, X.* “Site-selective and Metal-free Aliphatic C-H Oxidation Enabled Synthesis of [5,24,25-D3]-(25S)-Δ7-Dafachronic acid” Chem. Eur. J. 2015, 21, 5345-5379
  36. Hong, B.; Li, H.; Wu, J.; Zhang, J. Lei, X.* “Total Syntheses of (-)-Huperzine Q and (+)-Lycopladines B and C” Angew. Chem. Int. Ed. 2015, 54, 1011-1015. (Highlighted by Synfacts 2015, 11, 0112)
  37. Zhang, J.; Chen, J.; Zhang, X.; Lei, X.* “Total Syntheses of Menisporphine and Daurioxoisoporphine C Enabled by Photoredox-Catalyzed Direct C–H Arylation of Isoquinoline with Aryldiazonium Salt” J. Org. Chem. 2014, 79, 10682-10688
  38. Li, C.; Dong, T.; Li, Q.; Lei, X.* “Probing the Anti-cancer Mechanism of (-)-Ainsliatrimer A through Diverted Total Synthesis and Bioorthogonal Ligation” Angew. Chem. Int. Ed. 2014, 53, 12111-12115
  39. Zhang, J.; Wu, J.; Hong, B.; Ai, W.; Wang, X.; Li, H.; Lei, X.* “Diversity-oriented synthesis of Lycopodium alkaloids inspired by the hidden functional group pairing pattern” Nature Commun. 2014, 5, 4614
  40. Han, J.; Li, X.; Guan, Y.; Zhao, W.; Wullf, W. D.*; Lei, X.* “Enantioselective Biomimetic Total Syntheses of Kuwanons I and J and Brosimones A and B” Angew. Chem. Int. Ed. 2014, 53, 9257-9261
  41. Li, C.; Lei, X.* “Strategies toward the Biomimetic Syntheses of Oligomeric Sesquiterpenoids” J. Org. Chem. 2014, 79, 3289-3295
  42. Liao, D.; Sun, L.; Liu, W.; He, S.; Wang, X.; Lei, X.* “Necrosulfonamide Inhibits Necroptosis by Selectively Targeting the Mixed Lineage Kinase Domain-like Protein” Med. Chem. Comm. 2014, 5, 333-337.
  43. Li, Q.; Dong, T.; Liu, X.; Zhang, X.; Yang, X.; Lei, X.* “ortho-Quinone Methide Finds Its Application in Bioorthogonal Ligation” Curr. Org. Chem. 2014, 18, 86-92.
  44. 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.
  45. Wang, X.; Li, H.; Lei, X.* “Challenges and Strategies to the Total Syntheses of Fawcettimine-Type and Serratinine-Type Lycopodium Alkaloids” Synlett. 2013, 24,1032-1043 (Invited Synpacts Article).
  46. 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).
  47. 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.
  48. 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” Nature Chem. Biol. 2013, 9, 84-89. (News stories describing this work were highlighted in Chem. & Eng. News 2013, 2, 37; Nature Asia 2012, December 24).
  49. 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).
  50. 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.
  51. Lei, X.*; Li, H. “Selective Alkene Metathesis in the Total Synthesis of Complex Natural Product” Top. Curr. Chem. 2012, 327, 163-196.
  52. 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).
  53. 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.
  54. 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.
  55. 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.
  56. Li, C.; Yu, X.; Lei, X.* “A Biomimetic Total Synthesis of (+)-Ainsliadimer A” Org. Lett. 2010, 12, 4284-4287.
  57. 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.
  58. 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.
  59. 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. USA 2011, 108, 14336-14341.
  60. 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
  61. Lei, X.; Dai, M.; Hua, Z.; Danishefsky, S. J.* “Biomimetic Total Synthesis of Tricycloillicinone and Mechanistic Studies Toward the Rearrangement of Prenyl Phenyl Ethers” Tetrahedron Lett. 2008, 49, 6383-6385
  62. 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.)
  63. 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)
  64. 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.
  65. 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.
  66. 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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