分子细胞生物学

倪建泉

清华大学基础医学院院长助理,教授

Contact Us:
E-mail: nijq@tsinghua.edu.cn
Address:中国北京市海淀区清华大学生物医学影像研究中心211

教育背景

1996-2000 北京大学 硕士

2001-2006 瑞士巴塞尔大学 博士

工作经历

2006-2007 哈佛大学医学院/霍华德休斯医学研究所 博士后

2007-2008 JFRC/霍华德休斯医学研究所 研究助理

2009-2010 哈佛大学医学院/霍华德休斯医学研究所 助理研究员

2010-2014 清华大学医学院 助理教授2015-2016 清华大学医学院 副教授

2016-2021 清华大学医学院 长聘副教授

2021-2024 清华大学医学院 长聘教授

2024-现在 清华大学基础医学院 长聘教授

研究领域

基因调控与基因功能研究。从事果蝇遗传学工具的开发及应用,在果蝇中先后开发了基因组编辑技术、转录激活系统、转录抑制系统和新一代转基因干扰技术,并利用这些技术,深入探究了果蝇发育及干细胞稳态维持的表观调控机制。本实验室主要通过分子生物技术,结合细胞生物学、生物化学、多组学等技术,研究发育代谢、干细胞稳态维持等过程中相关基因发挥的重要功能及各种互作事件,探究基因互作事件在各类生命事件中扮演的角色,同时积极开展基于基因功能的潜在分子靶标的发现与开发。

科学贡献

开发并优化了基于CRISPR/Cas9的果蝇基因组编辑系统(PNAS,2013,通讯作者;Cell Reports,2014,通讯作者),实现高效、特异的基因组定点编辑,并被国内外实验室广泛应用。构建了Cas9单链切割酶的编辑技术,实现了基因组的精确编辑(G3,2014,通讯作者)。开发了两代果蝇中CRISPR/dCas9 介导的转录激活系统,并利用最新研发的flySAM系统实现了目的基因的特异、高效激活(PNAS,2017,通讯作者;PNAS,2018,通讯作者;G3,2020,通讯作者;),以此技术为基础的转基因转录激活资源库正在构建中,这是世界上第一个果蝇转基因过表达资源库,将为基因功能研究提供重要的技术资源,推动整个领域的快速发展。研发了新一代转基因干扰技术,与之前技术对比,具有毒副作用小、干扰效率高、背景表达低等优点,且突破性地实现多个基因的同时干扰(Nature methods,一作;Nature Communications,通讯作者)。利用此技术,构建了与人类疾病基因高度同源的转基因干扰资源库。另一方面,建立果蝇存储中心,在果蝇日常饲养、品系开发和种质保存等方面建立了标准化的操作体系(LABORATORY ANIMAL SCIENCE,2016,通讯作者)。

代表性论文(# 通讯作者,*一作)

1. Y Han, B Xu, Y Li, X Lu, J Sun, Q Liu, JQ Ni# , Cutting-edge gene regulatory systems in Drosophila, Hereditas, invited review

2. J Sun, X Wang, R Xu, D Mao, D Shen, X Wang, Y Qiu, Y Han, P Peng, X Kang, R Zhu, Y Jia, X Lu, Y Li, J Yu, Y Wang, L Liu, Z Chang, J Ji, Z Wang, QLiu, S Li#, F Sun#, JQ Ni#,HP1c regulates development and gut homeostasis by suppressing Notch signaling through Su(H),EMBO Report,Accepted

3. D Mao, Y Jia, P Peng, D Shen, X Ren, R Zhu, Y Qiu, Y Han, J Yu, Q Che, Y Li, X Lu, L Liu, Z Wang, Q Liu, Jin Sun# and JQ Ni#, Enhanced Efficiency of flySAM by Optimization of sgRNA Parameters in Drosophila, GENES GENOM GENET, 2020, doi.org/10.1534

4. Z Li, K Xu, S Zhao, Y Guo, H Chen, JQ Ni, Q Liu, ZWang#, SPATA4 improves aging-induced metabolic dysfunction through promotion of preadipocyte differentiation and adipose tissue expansion, Aging cell, 2020 Dec 13;e13282.

5. L Sun, L Cui, Z Liu, Q Wang, Z Xue, M Wu, T Sun, D Mao, JQ Ni, JC Pastor-Pareja, X Liang#, Katanin p60-like 1 sculpts the cytoskeleton in mechanosensory cilia, J Cell Biol, December 02 2020, 220 (1): e202004184.

6. X Li, M Liu, X Ren, N Loncle, Q Wang, R Waduge, S Yu, M Boube, H Bourbon, JQ Ni, JY Ji#, The Mediator CDK8-Cyclin C complex modulates Dpp signaling in Drosophila by stimulating Mad-dependent transcription, PLOS GENETICS, 2020 May 28;16(5):e1008832. doi: 10.1371

7. Y chen, T Sun, Z Bi, JQ ni, JC. pastor-pareja#,B Javid#,Premature termination codon readthrough in Drosophila varies in a developmental and tissue-specific manner, Scientific Reports, May 2020, doi.org/10.1038/s41598-020-65348-8

8. Zirin, J; Hu, Y; Liu, L; Yang D; C Ryan; Y Dong; E, Ben; T Rong; V Eric; V Sara; C Cooper; V Christians; C Aram; Sun, J; Wang, X; Jia, Yu; Zhu, R; Peng, P; Yu, J; Shen, D; Qiu, Y; Ayisi,d; R Henna; F Ethan; E Senait; P Annette; S Kuniaki; K Shu; P Liz; M Stephanie; Ni, JQ; P, Norbert#, Large-Scale Transgenic Drosophila Resource Collections for Loss- and Gain-of-Function Studies, Genetics, 2020 Apr;214(4):755-767.doi: 10.1534

9. Li Z, Xu K, Guo Y, Ping L, Gao Y, Qiu Y, Ni JQ, Liu Q, Wang Z#, A high-fat diet reverses metabolic disorders and premature aging by modulating insulin and IGF1 signaling in SIRT6 knockout mice, Aging Cell, 2020 Mar; 19(3):e13104

10. Sapiro L; Freund E; Restrepo L; Qiao HH; Bhate A; Li Q; Ni JQ; Mosca, T; Li, JB#, Zinc Finger RNA-Binding Protein Zn72D Regulates ADAR-Mediated RNA Editing in Neurons, Cell Reports, Volume 31, Issue 7, 19 May 2020, 107654

11. MAO Y, Tu R, Huang Y, Mao D, Yang Z, Lau P, Ni JQ#, Guo Y#, Xie T#,The Exocyst Functions in Niche Cells to Promote Germline Stem Cell Differentiation by Directly Controlling EGFR Membrane Trafficking, Development, 2019, 146: dev174615 doi: 10.1242

12. X Wang, D Shen, H Qiao, J Sun, R Xu, Q Liu, JQ Ni#, Guidance for Drosophila Culture and Management, Bio-101, 2019/06/20

13. Sun T, Song Y, Dai J, Mao D, Ma M, Ni JQ, Liang X, Pastor-Pareja J#, Spectraplakin Shot maintains perinuclear microtubule organization in Drosophila polyploid cells, Developmental Cell, April 18, 2019

14. Wang, F, Qiao, HH, Xu, R, Sun J, Zhu RB, Mao D, Ni, JQ# pNP Transgenic RNAi System Manual in Drosophila. BIO-PROTOCOL. Feb 5 2019. 9(3)

15. Xu RG, Wang X, Shen D, Sun J, Qiao H, Wang F, Liu LP, Ni JQ#, Perspectives of gene regulation in Drosophila, J Genet Genomics. 2019.03.006, DOI:org/10.1016/j.jgg

16. Peng P, Wang X, Shen D, Sun J, Jia Y, Xu RG, Zhu LF and Ni JQ#, CRISPR-Cas9 Mediated Genome Editing in Drosophila, Bio-protocol, Jan 20 2019. 9(2)

17. Y Gao; Y Mao; R.G Xu; R Zhu; M Zhang; J Sun; D Shen; P Peng; T Xie#, JQ Ni#, Defining Gene Networks Controlling the Maintenance and Function of the Differentiation Niche by an in vivo Systematic RNAi Screen, J Genet Genomics. Jan 20 2019. 46(1) 19-13.

18. Jia Y, Shen D, Wang X, Sun J, Peng P, Xu RG, Xu BW, Ni JQ#, flySAM Transgenic CRISPRa System Manual. BIO-PROTOCOL. Jan 20 2019. 9(2)

19. Qiao HH, Wang F, Xu RG, Sun J, Zhu R, Mao D, Ren X, Wang X, Jia Y, Peng P, Shen D, Liu LP, Chang Z, Wang G, Li S, Ji JY, Liu Q, Ni JQ# An efficient and multiple target transgenic RNAi technique with low toxicity in Drosophila, NATURE COMMUNICATIONS, 2018 Oct 8;9(1):4160. doi: 10.1038/s41467-018-06537-y.

20. Zheng Y, Xue Y, Ren X, Liu M, Li X, Jia Y, Niu Y, Ni J.Q#, Zhang Y#, Ji JY#. The Lysine Demethylase dKDM2 Is Non-essential for Viability, but Regulates Circadian Rhythms in Drosophila. Front Genet. 2018 Sep 4;9:354. doi: 10.3389/fgene.2018.00354.

21. Sapar ML, Ji H, Wang B, Poe AR, Dubey K, Ren X, Ni J.Q, Han C#. Phosphatidylserine Externalization Results from and Causes Neurite Degeneration in Drosophila. Cell Rep. 2018 Aug 28;24(9):2273-2286. doi: 10.1016/j.celrep.2018.07.095.

22. Xu R, Wang X, Wang F,Sun J, Mao D, Qiao H, Jia Y, Zhu R, Peng P, Liu LP, Ni JQ# Techniques and resource in DrosophilaACTA LABORATORIUM ANIMAL SCIENTIA SINICA (in Chinese), August 2018, Vol. 26, No. 4

23. Ke H, Feng Z, Liu M, Sun T, Dai J, Ma M, Liu LP, Ni JQ, Pastor-Pareja JC#. Collagen secretion screening in Drosophila supports a common secretory machinery and multiple Rab requirements. J Genet Genomics. 2018 Jun 1. doi: 10.1016/j.jgg.2018.05.002.

24. Wang X, Sun J, Wang F, Qiao H, Mao D, Ni JQ# The generation of novel transgenic lines and applications, Medical science (in Chinese),DOI:10.3772/j.issn.1673-6516.2018.07.022

25. Jia Y,Xu R,Sun J, Ni JQ# The specific and efficient CRISPR/dCas9 targeting activator—flySAM system, Hereditas, 2018, 5, 40(5): 425―427

26. Y Jia, R.G Xu, X Ren, B Ewen-Campen, R Rajakumar, J Zirin, D Yang-Zhou, R Zhu, F Wang, DMao, P Peng, H.H Qiao, X Wang, L.P Liu, B Xu, J.Y Ji, Q Liu, J Sun#, N Perrimon#, Ni J.Q#, Next-generation CRISPR/Cas9 transcriptional activation in Drosophila using flySAM, Proc Natl Acad Sci USA. 2018 May 1;115(18):4719-4724. doi: 10.1073/pnas.1800677115.

27. Ewen-Campen, B., Yang-Zhou, D., Fernandes, V.R., Gonzalez, D.P., Liu, L.P., Tao, R., Ren, X., Sun, J., Hu, Y., Zirin, J., Mohr, S.E., Ni J.Q#, and Perrimon, N#. Optimized strategy for in vivo Cas9-activation in Drosophila. Proc Natl Acad Sci USA. 2017 Aug 29;114(35):9409-9414. doi: 10.1073/pnas.1707635114.

28. Ren X, Holsteens K, Li H, Sun J, Zhang Y, Liu LP, Liu Q, Ni J.Q#. Genome editing in Drosophila melanogaster: from basic genome engineering to the multipurpose CRISPR-Cas9 system. Sci China Life Sci. 2017 May;60(5):476-489. doi: 10.1007/s11427-017-9029-9.

29. Yang, Z., Sun, J., Hu, Y., Wang, F., Wang, X., Qiao, H.H., Xu, J., Mao, D., Ren, X., Pan, L.X., Xu, R.G., Xu, B.W., Zhang, Y., Li, H., Miao, W., Hu, Y., Chang, Z., Wang, D., Li, H., Chang, Z., Liu, L.P., Liu, Q., Ni, J.Q#. Histone H1 defect in escort cells triggers germline tumor in Drosophila ovary. Developmental biology. 2017 Apr 1;424(1):40-49. doi: 10.1016/j.ydbio.2017.02.012.

30. Ma X, Han Y, Song X, Do T, Yang Z, Ni JQ, Xie T#. DNA damage-induced Lok/CHK2 activation compromises germline stem cell self-renewal and lineage differentiation. Development. 2016 Dec 1;143(23):4312-4323.

31. Xiong XP, Kurthkoti K, Chang KY, Li JL, Ren X, Ni JQ, Rana TM, Zhou R#. miR-34 Modulates Innate Immunity and Ecdysone Signaling in Drosophila. PLoS Pathog, 2016,12(11):e1006034

32. Wang X, Qiao H, Pan L, Ren X, Sun J, Xu R, Liu LP, He Z, NI JQ#, The generation and maintenance of transgenic flies, LABORATORY ANIMAL SCIENCE,Vol.33 No.3 June 2016

33. Lu T, Wang S, Gao Y, Mao Y, Yang Z, Liu L, Song X, Ni JQ#, Xie T#. COP9-Hedgehog Axis Regulates the Function of the Germline Stem Cell Progeny Differentiation Niche in the Drosophila Ovary, Development. 2015 Dec 15;142(24):4242-52. doi: 10.1242/dev.124768.

34. Sun J, Wei HM, Xu J, Chang JF, Yang Z, Ren X, Lv WW, Liu LP, Pan LX, Wang X, Qiao HH, Zhu B, Ji JY, Yan D, Xie T, Sun FL#, Ni JQ#. Histone H1-Mediated Epigenetic Regulation Controls Germline Stem Cell Self-Renewal by Modulating H4K16 Acetylation, Nature Communications. 2015 Nov 19;6:8856. doi: 10.1038/ncomms9856.

35. Fu Z, Geng C, Wang H, Yang Z, Weng C, Li H, Deng L, Liu L, Liu N, Ni JQ, Xie T# Twin Promotes the Maintenance and Differentiation of Germline Stem Cell Lineage through Modulating Multiple Pathways, Cell Reports. Epub 2015, Nov 5.

36. Pan L, Xie W, Li KL, Yang Z, Xu J, Zhang W, Liu LP, Ren X, He Z, Wu J, Sun J, Wei HM, Wang D, Xie W, Li W, Ni JQ#, Sun FL#. Heterochromatin remodeling by CDK12 contributes to learning in Drosophila, Proc Natl Acad Sci USA. 2015 Nov 10;112(45):13988-93. doi: 10.1073/pnas.1502943112.

37. Wang S, Gao Y, Song X, Ma X, Zhu X, Mao Y, Yang Z, Ni JQ, Li H, Malanowski KE, Anoja P, Park J, Haug J, Xie T#. Wnt signaling-mediated redox regulation maintains the germ line stem cell differentiation niche, ELife. October 9, 2015

38. Perkins LA, Holderbaum L, Tao R, Hu Y, Sopko R, McCall K, Yang-Zhou D, Flockhart I, Binari R, Shim HS, Miller A, Housden A, Foos M, Randkelv S, Kelley C, Namgyal P, Villalta C, Liu LP, Jiang X, Huan-Huan Q, Wang X, Fujiyama A, Toyoda A, Ayers K, Blum A, Czech B, Neumuller R, Yan D, Cavallaro A, Hibbard K, Hall D, Cooley L, Hannon GJ, Lehmann R, Parks A, Mohr SE, Ueda R, Kondo S, Ni JQ, Perrimon N#. The Transgenic RNAi Project at Harvard Medical School: Resources and Validation, Genetics. 2015 Aug 28. pii: Genetics.115.180208.

39. Xie XJ, Hsu FN, Gao X, Xu W, Ni JQ, Xing Y, Huang L, Hsiao HC, Zheng H, Wang C, Zheng Y, Xiao li AM, Yang F, Bondos SE, Ji JY#. CDK8-Cyclin C Mediates Nutritional Regulation of Developmental Transitions through the Ecdysone Receptor in Drosophila, PLoS Biology. 2015 Jul 29;13(7):e1002207.

40. Zang Y, Wan M, Liu M, Ke H, Ma S, Liu LP, Ni JQ, Pastor-Pareja JC#. Plasma membrane overgrowth causes fibrotic collagen accumulation and immune activation in Drosophila adipocytes, Elife. 2015 Jun 19;4:e07187.

41. Xu J, Ren X, Sun J, Wang X, Qiao HH, Xu BW, Liu LP, Ni JQ#, A Toolkit of CRISPR-Based Genome Editing Systems in Drosophila, J Genet Genomics. 2015 Apr 20;42(4):141-9.

42. Ren X, Yang Z, Xu J, Sun J, Mao D, Hu Y, Yang SJ, Qiao HH, Wang X, Hu Q, Deng P, Liu LP, Ji JY, Li JB#, Ni JQ#, Enhanced specificity and efficiency of the CRISPR/Cas9 system with optimized sgRNA parameters in Drosophila. Cell Reports. 2014 Nov 6;9(3):1151-62.

43. Ren X, Yang Z, Mao D, Chang Z, Qiao HH, Wang X, Sun J, Hu Q, Cui Y, Liu LP, Ji JY, Xu J, Ni JQ#. Performance of the Cas9 Nickase System in Drosophila melanogaster. G3 (Bethesda). 2014 Aug 15;4(10):1955-62.

44. Pan L, Wang S, Lu T, Weng C, Song X, Park JK, Sun J, Yang ZH, Yu J, Tang H, McKearin DM, Chamovitz DA, Ni JQ, Xie T#. Protein competition switches the function of COP9 from self-renewal to differentiation. Nature. 2014 Oct 9;514(7521):233-6.

45. Zheng Y, Hsu FN, Xu W, Xie XJ, Ren X, Gao X, Ni JQ, Ji JY#. A Genetic Analysis of the Lysine Demethylase KDM2 in Drosophila melanogaster. Mech Dev. 2014 Aug;133:36-53.

46. Ma X, Wang S, Do T, Song X, Inaba M, Nishimoto Y, Liu LP, Gao Y, Mao Y, Li H, McDowell W, Park J, Malanowski K, Peak A, Perera A, Li H, Gaudenz K, Haug J, Yamashita Y, Lin H, Ni JQ, Xie T#. Piwi is required in multiple cell types to control germline stem cell lineage development in the Drosophila ovary. PLoS One. 2014 Mar 21;9(3):e90267.

47. Ren X, Sun J, Housden BE, Hu Y, Roesel C, Lin S, Liu LP, Yang Z, Mao D, Sun L, Wu Q, Ji JY, Xi J, Mohr SE, Xu J#, Perrimon N#, Ni JQ#. An optimized gene editing technology for Drosophila melanogaster using germline-specific Cas9, Proc Natl Acad Sci USA. 2013 Nov 19;110(47):19012-7.

48. Y Yang, L Hou, Y Li, NI JQ and L Liu#, Neuronal necrosis and spreading death in a Drosophila genetic model, Cell Death and Disease, 2013, (2013) 4, e723.

49. Lv WW, Wei HM, Wang DL, Ni JQ, Sun FL#. Depletion of histone deacetylase 3 antagonizes PI3K-mediated overgrowth through the acetylation of histone H4 at lysine 16. J Cell Sci. 2012 Nov 15;125(Pt 22):5369-78.

50. Bejarano F, Bortolamiol-Becet D, Dai Q, Sun K, Saj A, Chou YT, Raleigh DR, Kim K, Ni JQ, Duan H, Yang JS, Fulga TA, Van Vactor D, Perrimon N, Lai EC#. A genomewide transgenic resource for conditional expression of Drosophila microRNAs. Development. 2012 Aug;139(15):2821-31.

51. Zhao X, Feng D, Wang Q, Abdulla A, Xie XJ, Zhou J, Sun Y, Yang ES, Liu LP, Vaitheesvaran B, Bridges L, Kurland IJ, Strich R, Ni JQ, Wang C, Ericsson J, Pessin JE, Ji JY#, Yang F#. A Conserved Function of CDK8 in Suppressing SREBP-dependent Lipogenesis. Journal of Clinical Investigation. 2012 Jul 2;122(7):2417-27.

52. Ni JQ, Zhou R, Czech B, Liu LP, Holderbaum L, Yang-Zhou D, Shim HS, Tao R, Handler D, Karpowicz P, Binari R, Booker M, Brennecke J, Perkins LA, Hannon GJ, Perrimon N#. A genome-scale shRNA resource for transgenic RNAi in Drosophila . Nature Methods. 2011 May;8(5):405-7.

53. Perrimon N#, Ni JQ, Perkins L. In vivo RNAi: Today and Tomorrow. Cold Spring Harbor Perspectives in Biology. 2010 Aug 1;2(8):a003640.

54. Ni JQ, Liu LP, Binari R, Hardy R, Shim HS, Cavallaro A, Booker M, Pfeiffer BD, Markstein M, Wang H, Villalta C, Laverty TR, Perkins LA, Perrimon N#. A Drosophila Resource of transgenic RNAi lines for Neurogenetics. Genetics. 2009 Aug;182(4):1089-100.

55. Bai J, Binari R, Ni JQ, Vijayakanthan M, Li HS, Perrimon N#. RNA interference screening in Drosophila primary cells for genes involved in muscle assembly and maintenance. Development. 2008 Apr;135(8):1439-49.

56. Ni JQ, Markstein M, Binari R, Pfeiffer B, Liu LP, Villalta C, Booker M, Perkins L, Perrimon N#. Vector and parameters for targeted transgenic RNA interference in Drosophila melanogaster. Nature Methods. 2008 January; 5(1): 49–51.

57. Ni JQ, Liu LP, Hess D, Rietdorf J, Sun FL#. Drosophila ribosomal proteins are associated with chromatin through histone H1 and suppress global transcription. Genes Development. 2006 Jul 15;20(14):1959-73.

58. Cen X, Ni JQ, Tan T, Liu X, Li C, Chen J, Huang Y, Zhu S, Bi Q#. Investigation on recombinant hirudin via oral route. Peptides. 2006 Apr;27(4):836-40. Epub 2006 Feb 13.

59. Liu LP*, Ni JQ*, Shi YD, Oakeley EJ, Sun FL#. Sex-specific role of Drosophila melanogaster HP1 in regulating chromatin structure and gene transcription. Nature Genetics. 2005 Dec; 37(12):1361-6. (*co-first author)

60. De LF, Ni JQ, Vaillant C, Sun FL#. HP1 modulates the transcription of cell-cycle regulators in Drosophila melanogaster. Nucleic Acids Res. 2005. 33(9): 2852-8.


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