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 |
永利集团 |
理学学士(化学) |
导师:王剑波 教授 |
工作背景:
2017-现在 |
永利集团 77779193永利集团 |
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 |
永利集团 77779193永利集团 |
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:
- Bristol Myers Squibb Lectureship, Yale University, 2025
- Distinguished Visiting Professorship, Kyoto University, 2024
- Sackler Chair Visiting Scholar Award, Israel, 2023
- 科学探索奖,2022
- 屠呦呦奖,2022
- Boehringer-Ingelheim Senior Faculty Research Award, 2021
- Novartis Most Valuable Partner Award, 2021
- 教育部长江学者特聘教授,2021
- Bayer Investigator Award, 2020
- 树兰医学青年奖,2019
- 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
- 国际化员工物学协会(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:
有机合成、化员工物学、生物催化、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:
- 利用化员工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:
- Pei Miao, Haijun Wang, Wei Wang, Zhengdong Wan, Han Ke, Hangyuan Chen, Jinjing Ni, Jingnan Liang, Yu-Feng Yao, Jizong Wang, Jian-Min Zhou*, and Xiaoguang Lei*“A widespread plant defense compound disarms bacterial type III injectisome assembly” Science 2025, 387, eads0377 (Highlighted by C&E News)
- Jun Yang, Tianjun Zhao, Junping Fan, Huaibin Zou, Guangyi Lan, Fusheng Guo Yaocheng Shi, Han Ke, Huasheng Yu, Zongwei Yue, Xin Wang, Yingjie Bai, Shui Li, Yingjun Liu, Xiaoming Wang, Yu Chen*, Yulong Li*, Xiaoguang Lei* “Structure-guided discovery of bile acid derivatives for treating liver diseases without causing itch” Cell 2024, 187, 7164–7182 (Highlighted by C&E News)
- Lei Li, Zhengping Ge, Shihao Liu, Kun Zheng, Yaqi Li, Kaiqi Chen, Yesheng Fu, Xiaoguang Lei, Zeling Cui, Yifan Wang, Jin Huang, Yanyan Liu, Mingwang Duan, Zimei Sun, Jun Chen, Liangwei Li, Pan Shen, Guibin Wang, Junmiao Chen, Ruochong Li, Chaoran Li, Zhixiang Yang, Yifan Ning, Arong Luo, Baoyu Chen, Inge Seim, Xin Liu, Fei Wan, Yishan Yao, Fusheng Guo, Maojun Yang, Cui Hua Liu, Guangyi Fan*, Lizhi Wang*, Dong Yang*, Lingqiang Zhang* “Multi-omics landscape and molecular basis of radiation tolerance in a tardigrade” Science 2024, 386, eadl0799
- Haoran Dong, Nianxin Guo, Dachao Hu, Benke Hong, Daohong Liao, Hong Jie Zhu, Zhang Yuan Yan, Hui Ming Ge, Xiaoguang Lei* “Chemoenzymatic Total Synthesis of Alchivemycin A” Nature Synthesis, 2024, 3, 1124-1133 (Highlighted by C&E News)
- Lei Gao, Qi Ding, Xiaoguang Lei* “Hunting for the intermolecular Diels-Alderase” Acc. Chem. Res. 2024, 57, 2166–2183 (Cover article)
- Bin Jiang, Lei Gao, Haijun Wang, Yaping Sun, Xiaolin Zhang, Han Ke, Shengchao Liu, Pengchen Ma, Qinggang Liao, Yue Wang, Huan Wang, Yugeng Liu, Ran Du, Torben Rogge, Wei Li, Yi Shang, K. N. Houk, Xingyao Xiong, Daoxin Xie, Sanwen Huang, Xiaoguang Lei*, Jianbin Yan* “Characterization and heterologous reconstitution of Taxus biosynthetic enzymes leading to baccatin III” Science 2024, 383, 622-629. (Highlighted by C&E News)
- Kai Wang, Zhiwei Zhang, Jing Hang, Jia Liu, Fusheng Guo, Yong Ding, Meng Li, Qixing Nie, Jun Lin, Yingying Zhuo, Lulu Sun, Qihang Zhong, Chuan Ye, Chuyu Yun, Yi Zhang, Jue Wang, Rui Bao, Yanli Pang, Guang Wang*, Frank J. Gonzalez*, Xiaoguang Lei*, Jie Qiao*, Changtao Jiang* “Microbial-host-isozyme analyses reveal microbial DPP4 inhibition as a potential antidiabetic target”Science 2023, 381, eadd5787
- Junping Fan, Linghan Hu, Zongwei Yue, Daohong Liao, Fusheng Guo, Han Ke, Daohua Jiang*, Yong Yang*, Xiaoguang Lei* “Structural basis of TRPV3 inhibition by an antagonist” Nature Chemical Biology 2023, 19, 81-90
- Jianyong Du, Lixia Zheng, Peng Gao, Hang Yang, Wan-Jie Yang, Fusheng Guo, Ruqi Liang, Mengying Feng, Zihao Wang, Zongwang Zhang, Linlu Bai, Ye Bu, Shijia Xing, Wen Zheng, Xuelian Wang, Li Quan, Xinli Hu, Haosen Wu, Zhixing Chen, Liangyi Chen, Ke Wei, Zhe Zhang, Xiaojun Zhu, Xiaolin Zhang, Qiang Tu, Shi-Min Zhao*, Xiaoguang Lei*, Jing-Wei Xiong* “A small-molecule cocktail promotes mammalian cardiomyocyte proliferation and heart regeneration” Cell Stem Cell 2022, 29, 545-558
- Lei Gao, Yike Zou, Xiaojing Liu, Jun Yang, Xiaoxia Du, Jin Wang, Xinshui Yu, Junping Fan, Mingxuan Jiang, Yuli Li, K. N. Houk*, Xiaoguang Lei* “Enzymatic control of endo and exo stereoselective Diels-Alder reactions with broad substrate scope” Nature Catalysis 2021, 4, 1059-1069
- Weilong Liu, Benke Hong, Jin Wang, Xiaoguang Lei* “New Strategies in the Efficient Total Syntheses of Polycyclic Natural Products” Acc. Chem. Res. 2020, 53, 2569–2586
- Lei Gao, Cong Su, Xiaoxia Du, Ruishan Wang, Shuming Chen, Yu Zhou, Chengwei Liu, Xiaojing Liu, Runze Tian, Liyun Zhang, Kebo Xie, She Chen, Qianqian Guo, Lanping Guo, Yoshio Hano, Manabu Shimazaki, Atsushi Minami, Hideaki Oikawa, Niu Huang, K. N. Houk, Luqi Huang*, Jungui Dai*, Xiaoguang Lei* "FAD-dependent Enzyme-Catalysed Intermolecular [4+2] Cycloaddition in Natural Product Biosynthesis" Nature Chemistry, 2020, 12, 620-628. (Highlighted by Chemistry World)
- Wang W, Yang J, Zhang J, Liu YX, Tian C, Qu B, Gao C, Xin P, Cheng S, Zhang W, Miao P, Li L, Zhang X, Chu J, Zuo J, Li J, Bai Y, Lei X,* Zhou JM* “An Arabidopsis Secondary Metabolite Directly Targets Expression of the Bacterial Type III Secretion System to Inhibit Bacterial Virulence” Cell Host & Microbe 2020, 27, 601–613
- Bai, Y.; Lam, H.C.; Lei, X.*“Dissecting Programmed Cell Death with Small Molecules” Acc. Chem. Res. 2020, 53, 1034-1045
- Wang J, Hong B, Hu D, Kadonaga Y, Tang R, Lei X.* “Protecting-Group-Free Syntheses of ent-Kaurane Diterpenoids: [3+2+1] Cycloaddition/Cycloalkenylation Approach.” J. Am. Chem. Soc. 2020, 142, 2238-2243
- Sourav Banerjee, Tiantian Wei, Jue Wang, Jenna J. Lee, Haydee L. Gutierrez, Owen Chapman, Sandra E. Wiley, Joshua E. Mayfield, Vasudha Tandon, Edwin F. Juarez, Lukas Chavez, Ruqi Liang, Robert L. Sah, Caitlin Costello, Jill P. Mesirov, Laureano de la Vega, Kimberly L. Cooper, Jack E. Dixon*, Junyu Xiao*, and Xiaoguang Lei* “Inhibition of dual-specificity tyrosine phosphorylation-regulated kinase 2 perturbs 26S proteasome-addicted neoplastic progression” Proc. Natl Acad. Sci. USA 2019, 116, 24881-24891
- Benke Hong, Weilong Liu, Jin Wang, Jinbao Wu, Yuichiro Kadonaga, Pei-Jun Cai, Hong-Xiang Lou, Zhixiang Yu, Houhua Li*, Xiaoguang Lei* “Photoinduced Skeletal Rearrangements Reveal Radical-Mediated Synthesis of Terpenoids” Chem 2019, 6,1671-1681 (Featured Article)
- Zhuang, S.; Li, Q.; Cai, L.; Wang, C.*; Lei, X.* “Chemoproteomic Profiling of Bile Acid Interacting Proteins” ACS Cent. Sci. 2017, 3, 501-509
- 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
- 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
- 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)
- 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)
- 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
- 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)
- 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
- 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)
- 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)
- 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
- 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
- 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)