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雷鸣

执行院长,研究员,研究组长,博士生导师

研究方向:染色质结构与衰老分子机制
邮箱:leim@@shsmu.edu.cn
实验室链接:http://www.shipm.cn/jyjz_web/html/DefaultSite/jyjz_syxz_lmz_sysjj/List/index.htm

研究兴趣
雷鸣研究员长期致力于蛋白质复合体为主的生物大分子的结构和分子机理及其在癌症和衰老中的作用等科研工作,在染色体研究特别是端粒与端粒酶、表观遗传学、核糖核酸酶等领域作出了多项突破性的工作,受到了国际同行的广泛关注与认可。自建立独立实验室以来,在国际顶级学术期刊上发表论文70余篇,近五年来论文他引次数5000余次。
雷鸣研究员自2011年回国以后,承担多项国家级和省部级科研任务,作为首席科学家主持国家科技部973重大研究计划项目1项,主持国家基金委重点项目2项,主持国家基金委大科学装置联合基金项目1项,参与中科院战略性先导技术专项(B类)1项,参与国家科技部重大新药创制专项计划1项,参与国家科技部蛋白质科学重大研究计划项目2项,并得到2015年度“国家杰出青年科学基金”、2016年度“上海市优秀学科带头人”等人才项目支持。
个人教育经历与工作经历
教育经历:
1996/09–2001/05, 美国哈佛大学医学院, 生物物理学, 博士
1994/09–1996/05, 加拿大麦吉尔大学物理系, 物理学, 硕士
1989/09–1994/07, 清华大学现代应用物理系, 物理学与计算机科学,双学士

工作经历:
2017/09 – 至今, 上海交通大学医学院附属九院上海精准医学研究院,研究员
2011/06 – 2017/09,中科院上海生科院生化细胞所,研究员
2010/09 – 2011/06,美国密歇根大学医学院生物化学系,副教授
2009/01 – 2011/06,美国霍华德休斯医学研究院(HHMI),青年研究员
2004/11 – 2010/09,美国密歇根大学医学院生物化学系,助理教授
2001/11 – 2004/11,美国科罗拉多大学波尔德分校化学与生物化学系,博士后

行政兼职:
2017/09 – 至今, 上海交通大学医学院附属九院上海精准医学研究院,执行院长
2011/06 – 2017/09,中科院上海生科院生化细胞所,副所长
2011/06 – 2017/09,中科院上海生科院生化细胞所国家蛋白质科学中心(上海),主任
代表性研究成果

1. Lan P, Zhou B, Tan M, Li S, Cao M, Wu J*, and Lei M* Structural insight into precursor ribosomal RNA processing by ribonuclease MRP. Science. 2020, 369(6504): 656-663.

2. Ge Y#, Wu Z#,*, Chen H, Zhong Q, Shi S, Li G, Wu J*, and Lei M* Structural insights into telomere protection and homeostasis regulation by yeast CST complex. Nat Struct Mol Biol. 2020, 27(8): 752-762.

3. Lin X#, Li M#, Wang N#, Wu Y, Luo Z, Guo S, Han GW, Li S, Yue Y, Wei X, Xie X, Chen Y, Zhao S, Wu J*, Lei M*, and Xu F* Structural basis of ligand recognition and self-activation of orphan GPR52. Nature. 2020, 579(7797): 152-157.

4. Zhang C#, Shuai J#, Ran Z#, Zhao J, Wu Z, Liao R, Wu J*, Ma W*, and Lei M* Structural insights into NDH-1 mediated cyclic electron transfer. Nat Commun. 2020, 11(1): 888.

5. Wan B#, Wu J, Meng X, Lei M*, and Zhao X* Molecular Basis for Control of Diverse Genome Stability Factors by the Multi-BRCT Scaffold Rtt107. Mol Cell. 2019, 75(2): 238-251.

6. Wan F#, Wang Q#, Tan J#, Tan M, Chen J, Shi S, Lan P*, Wu J*, and Lei M* Cryo-electron microscopy structure of an archaeal ribonuclease P holoenzyme. Nat Commun. 2019, 10(1): 2617.

7. Wang Y#, Chen Y#, Chen J, Wang L, Nie L, Long J, Chang H, Wu J, Huang C*, and Lei M* The meiotic TERB1-TERB2-MAJIN complex tethers telomeres to the nuclear envelope. Nat Commun. 2019, 10(1): 564.

8. Wu J#, Niu S#, Tan M#, Huang C, Li M, Song Y, Wang Q, Chen J, Shi S, Lan P*, and Lei M* Cyro-EM structure of human ribonuclease P holoenzyme. Cell. 2018, 175(5): 1393-1404.

9. Lan P#, Tan M#, Zhang Y#, Niu S, Chen J, Shi S, Qiu S, Wang X, Peng X, Cai G, Cheng H, Wu J*, Li G*, and Lei M* Structural insight into precursor tRNA processing by yeast ribonuclease P. Science. 2018, 362(6415), pii: eaat6678.

10. Chen H#, Xue J#, Churikov D, Hass EP, Shi S, Lemon LD, Luciano P, Bertuch AA, Zappulla DC, Geli V, Wu J*, and Lei M* Structural insights into yeast telomerase recruitment to telomeres. Cell. 2018, 172(1-2), 331-43 e13.

11. Xue J#, Chen H#, Wu J, Takeuchi M, Inoue H, Liu Y, Sun H, Chen Y*, Kanoh J*, and Lei M* Structure of the fission yeast S. pombe telomeric Tpz1-Poz1-Rap1 complex. Cell Res. 2017, 27(12), 1503-20.

12. Hu C#, Rai R#, Huang C, Broton C, Long J, Xu Y, Xue J, Lei M*, Chang S*, and Chen Y* Structural and functional analyses of the mammalian TIN2-TPP1-TRF2 telomeric complex. Cell Res. 2017, 27(12), 1485-502.

13. Long J#, Huang C#, Chen Y, Zhang Y, Shi S, Wu L, Liu Y, Liu C, Wu J*, and Lei M* Telomeric TERB1-TRF1 interaction is crucial for male meiosis. Nat Struct Mol Biol. 2017, 24(12), 1073-80.

14. Chen C#, Gu P#, Wu J, Chen X, Niu S, Sun H, Wu L, Li N, Peng J, Shi S, Fan C, Huang M, Wong CCL, Gong Q, Kumar-Sinha C, Zhang R, Pusztai L, Rai R, Chang S*, and Lei M* Structural insights into POT1-TPP1 interaction and POT1 C-terminal mutations in human cancer. Nat Commun. 2017, 8:14929.

15. Rai R#, Hu C, Broton C, Chen Y, Lei M*, and Chang S* NBS1 phosphorylation status dictates repair choice of dysfunctional telomeres. Mol Cell. 2017, 65(5): 801-17.

16. Yin J#, Wan B#, Sarkar J#, Horvath K, Wu J, Chen Y, Cheng G, Wan K, Chin P, Lei M*, and Liu Y* Dimerization of SLX4 contributes to functioning of the SLX4-nuclease complex. Nucleic Acids Res. 2016, 44(10): 4871-80.

17. Li Y#, Han J, Zhang Y, Cao F, Liu Z, Li S, Wu J, Hu C, Wang Y, Shuai J, Chen J, Cao L, Li D, Shi P, Tian C, Zhang J, Dou Y, Li G*, Chen Y*, and Lei M* Structural basis for activity regulation of MLL family methyltransferases. Nature. 2016, 530(7591): 447-52.

18. Wan B#, Tang T#, Upton H, Shuai J, Zhou Y, Li S, Chen J, Brunzelle JS, Zeng Z, Collins K, Wu J*, and Lei M* The Tetrahymena telomerase p75-p45-p19 subcomplex is a unique CST complex. Nat Struct Mol Biol. 2015, 22(12): 1023-6.

19. Sarkar J#, Wan B, Yin J, Vallabhaneni H, Horvath K, Kulikowicz T, Bohr VA, Zhang Y, Lei M*, and Liu Y* SLX4 contributes to telomere preservation and regulated processing of telomeric joint molecule intermediates. Nucleic Acids Res. 2015, 43(12): 5912-23.

20. Deng W#, Wu J#, Wang F#, Kanoh J, Dehe PM, Inoue H, Chen J, and Lei M* Fission yeast telomere-binding protein Taz1 is a functional but not a structural counterpart of human TRF1 and TRF2. Cell Res. 2015, 25(7): 881-4.

21. Huang J#, Brown A, Wu J, Xue J, Bley C, Rand D, Wu L, Zhang R, Chen J*, and Lei M* Structural Basis for Protein-RNA Recognition in Telomerase. Nat Struct Mol Biol. 2014, 21(6): 507-12.

22. Wan B#, Yin J#, Horvath K#, Sarkar J, Chen Y, Wu J, Wan K, Lu J, Gu P, Yu EY, Lue NF, Chang S, Liu Y*, and Lei M* SLX4 assembles a telomere maintenance toolkit by bridging multiple endonucleases with telomeres. Cell Rep. 2013, 4(5): 861-9.

23. Yu EY#, Sun J#, Lei M*, and Lue NF* Analyses of Candida Cdc13 orthologues revealed a novel OB fold dimer arrangement dimerization-assisted DNA binding and substantial structural differences between Cdc13 and RPA70. Mol Cell Biol. 2012, 32(1): 186-98.

24. Huang J#, Wan B, Wu L, Yang Y, Dou Y, and Lei M* Structural insight into the regulation of MOF in the male-specific lethal complex and the non-specific lethal complex. Cell Res. 2012, 22(6): 1078-81.

25. Huang J#, Gurung B, Wan B, Matkar S, Veniaminova NA, Wan K, Merchant JL, Hua X*, and Lei M* The same pocket in menin binds both MLL and JUND but has opposite effects on transcription. Nature. 2012, 482(7386): 542-6.

26. Chen Y#, Cao F, Wan B, Dou Y, and Lei M* Structure of the SPRY domain of human Ash2L and its interactions with RbBP5 and DPY30. Cell Res. 2012, 22(3): 598-602.

27. Zeng Z#, Min B#, Huang J, Hong K, Yang Y, Collins K*, and Lei M* Structural basis for Tetrahymena telomerase processivity factor Teb1 binding to single-stranded telomeric-repeat DNA. Proc Natl Acad Sci U S A. 2011, 108(51): 20357-61.

28. Sun J#, Yang Y, Wan K, Mao N, Yu TY, Lin YC, DeZwaan DC, Freeman BC, Lin JJ, Lue NF, and Lei M* Structural bases of dimerization of yeast telomere protein Cdc13 and its interaction with the catalytic subunit of DNA polymerase alpha. Cell Res. 2011, 21(2): 258-74.

29. Chen Y#, Wan B#, Wang KC#, Cao F, Yang Y, Protacio A, Dou Y, Chang HY, and Lei M* Crystal structure of the N-terminal region of human Ash2L shows a winged-helix motif involved in DNA binding. EMBO Rep. 2011, 12(8): 797-803.

30. Chen Y#, Rai R#, Zhou ZR, Kanoh J, Ribeyre C, Yang Y, Zheng H, Damay P, Wang F, Tsujii H, Hiraoko Y, Shore D, Hu H, Chang S*, and Lei M* A conserved motif within RAP1 has diversified roles in telomere protection and regulation in different organisms. Nat Struct Mol Biol. 2011, 18(2): 213-21.

31. Zeng Z#, Wang W#, Yang Y, Chen Y, Yang X, Diehl JA, Liu X*, and Lei M* Structural basis of selective ubiquitination of TRF1 by SCFFbx4. Dev Cell. 2010, 18(2): 214-25.

32. Wang F#, Yang Y, Singh TR, Busygina V, Guo R, Wan K, Wang W, Sung P, Meetei AR, and Lei M* Crystal structures of RMI1 and RMI2 two OB-fold regulatory subunits of the BLM complex. Structure. 2010, 18(9): 1159-70.

33. Cao F#, Chen Y#, Cierpicki T, Liu Y, Basrur V, Lei M*, and Dou Y* An Ash2L/RbBP5 heterodimer stimulates the MLL1 methyltransferase activity through coordinated substrate interactions with the MLL1 SET domain. PLoS One. 2010, 5(11): e14102.

34. Wang W#, Yang Y, Gao Y, Xu Q, Wang F, Zhu S, Old W, Resing K, Ahn N, Lei M*, and Liu X* Structural and mechanistic insights into Mps1 kinase activation. J Cell Mol Med. 2009, 13(8B): 1679-94.

35. Sun J#, Yu EY#, Yang Y, Confer LA, Sun SH, Wan K, Lue NF*, and Lei M* Stn1-Ten1 is an Rpa2-Rpa3-like complex at telomeres. Genes Dev. 2009, 23(24): 2900-14.

36. Chen Y#, Yang Y, van Overbeek M, Donigian JR, Baciu P, de Lange T, and Lei M* A shared docking motif in TRF1 and TRF2 used for differential recruitment of telomeric proteins. Science. 2008, 319(5866): 1092-6.

37. Wang F#, Podell ER, Zaug AJ, Yang Y, Baciu P, Cech TR, and Lei M* The POT1-TPP1 telomere complex is a telomerase processivity factor. Nature. 2007, 445(7127): 506-10.

38. Chen Y#, Yang Y, Wang F, Wan K, Yamane K, Zhang Y, and Lei M* Crystal structure of human histone lysine-specific demethylase 1 (LSD1). Proc Natl Acad Sci U S A. 2006, 103(38): 13956-61.