首页 全所PI名录
  • 吴立刚
  • 研究员,研究组长,博士生导师
  • E-mail: lgwu@@sibcb.ac.cn
  • 实验室主页: 
    个人简介:
  •   1996年毕业于上海交通大学生物科学与技术系,获学士学位。2001年毕业于中国科学院上海植物生理研究所遗传学专业,获博士学位。2001年至2008年在美国纽约大学(NYU)医学院从事博士后研究。2008年10月起任中科院上海生科院生化与细胞所研究员。

    社会任职:
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    研究方向:
  • mRNA和非编码小RNA调控的分子机制、理性设计和转化应用
    研究工作:
  •   研究mRNA和非编码小RNA调控的分子机制、理性设计和转化应用。运用生物化学、分子生物学手段,结合高通量测序和生物信息学方法,从分子水平和RNA组学水平,研究mRNA和非编码小RNA在细胞命运决定、生殖细胞生成过程中的生物学功能和分子机制;运用获得的知识指导RNA分子机器的理性设计,开发新技术新方法,用于临床疾病诊治和工业化生产。

      研究内容包括:

      (1)mRNA在细胞中的稳定性调控的分子机制。

      (2)miRNA、siRNA、piRNA等非编码小RNA的功能和机制。

      (3)mRNA和siRNA(RNAi)药物和新疗法的开发。

      (4)单细胞小RNA/mRNA高通量测序技术和生信算法的开发和应用。

      (5)基因编辑复合物分子机器的改进及应用。

    承担科研项目情况:
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    代表论著:
    1. Zhou G, Gu Y, Zhu Z, Zhang H, Liu W, Xu B, Zhou F, Zhang M, Hua K*, Wu L*and Ding J*. Exosome Mediated Cytosolic Cisplatin Delivery Through Clathrin-Independent Endocytosis and Enhanced Anti-cancer Effect via Avoiding Endosome Trapping in Cisplatin-Resistant Ovarian Cancer.Frontiers in Medicine. 2022 May;9:810761
    2. Wang X#, Jiang Q#, Song Y#, He Z, Zhang H, Song M, Zhang X, Dai Y, Oezlem Karalay, Christoph Dieterich,Adam Antebi, Wu L*, Han J*,Shen Y*.Ageing induces tissue-specific transcriptomicchanges inCaenorhabditis elegans.The EMBO Journal, 2022 March; 41:e109633
    3. Zhang H#, Zhang F#, Chen Q#, Li M#, Lv X, Xiao Y, Zhang Z, Hou L, Lai Y, Zhang Y, Zhang A, Gao S, Fu H, Xiao W, Zhou J, Diao F, Shi A, Su Y, Zeng W*Wu L*, Li J*. The piRNA pathway is essential for generating functional oocytes in golden hamsters. Nature Cell Biology,2021 Sep;23(9):1013-1022
    4. Zhang Y#, Teng Y#, Xiao W, Xu B, Zhao Y*, Li W* and Wu L*, Identifying cleaved and noncleaved targets of small interfering RNAs and microRNAs in mammalian cells by SpyCLIP. Mol Ther Nucleic Acids. 2020 Dec 4; 22:900-909. 
    5. Zhu Z#, Zhang Y#, Wu L*, Hua K* and Ding J*, Regeneration-Related Functional Cargoes in Mesenchymal Stem Cell-Derived Small Extracellular Vesicles. Stem Cells Dev. 2020 Jan 1;29(1):15-24. 
    6. Yang Q#, Li R#, Lyu Q#, Hou L#, Liu Z, Sun Q, Liu M, Shi H, Xu B, Yin M, Yan Z, Huang Y, Liu M, Li Y and Wu L*. Single-cell CAS-seq reveals a class of short PIWI-interacting RNAs in human oocytes. Nat Commun. 2019 Jul 29;10(1):3389.
    7. Tang C, Ni M, Xie S, Zhang Y, Zhang C, Ni Z, Chu C, Wu L, Zhou Y, Zhang Y. DICER1 regulates antibacterial function of epididymis by modulating transcription of β-defensins. J Mol Cell Biol. 2019 May 1;11(5):408-420.
    8. Hua M#,Liu W#,Chen Y#,Zhang F,Xu B,Liu S,Chen G*,Shi H* and  Wu L*. Identification of small non-coding RNAs as sperm quality biomarkers for in vitro fertilization. Cell Discov. 2019 Arp 9; 5:20
    9. Zhao Y#, Zhang Y#, Teng Y, Liu K, Liu Y, Li W and Wu L* SpyCLIP: An easy-to-use and high-throughput compatible CLIP platform for characterization of protein-RNA interactions with high accuracy. Nucleic Acids Res. 2019 Apr 8;47(6):e33.
    10.  Zhang F#, Zhang Y#, Lv X, Xu B, Zhang H, Yan J, Li H, Wu L*. Evolution of an X-linked miRNA family predominantly expressed in mammalian male germ cells. Mol Biol Evol. 2019 Apr 1;36(4):663-678.
    11. Zhu Z, Zhang Y, Zhang Y, Zhang H, Liu W, Zhang N, Zhang X, Zhou G, Wu L*, Hua K*, Ding J*. Exosomes derived from human umbilical cord mesenchymal stem cells accelerate growth of VK2 vaginal epithelial cells through MicroRNAs in vitro. Hum Reprod. 2019 Feb 1;34(2):248-260.
    12. Zhang K, Zhang X, Cai Z, Zhou J, Cao R, Zhao Y, Chen Z, Wang D, Ruan W, Zhao Q, Liu G, Xue Y, Qin Y, Zhou B, Wu L, Nilsen T, Zhou Y*, Fu XD*. A novel class of microRNA-recognition elements that function only within open reading frames. Nat Struct Mol Biol. 2018 Nov;25(11):1019-1027.
    13. Xu Y, Sun Y, Shen H, Dai Y, Liu H, Li R, Zhang H, Wu L, Zhu X, Liu X*. Regulation of the terminal maturation of iNKT cells by mediator complex subunit 23. Nat Commun. 2018 Sep 24;9(1):3875.
    14. Peng L#, Zhang F#, Shang R#, Wang X, Chen J, Chou JJ, Ma J, Wu L*, Huang Y*. Identification of substrates of the small RNA methyltransferase Hen1 in mouse spermatogonial stem cells and analysis of its methyl-transfer domain. J Biol Chem. 2018 Jun 29;293(26):9981-9994.
    15. Zhang Y, Liu W, Li R, Gu J, Wu P, Peng C, Ma J, Wu L, Yu Y, Huang Y. Structural insights into the sequence-specific recognition of Piwi by Drosophila Papi. Proc Natl Acad Sci.  2018 Mar 27;115(13):3374-3379.
    16. Long J, Huang C, Chen Y, Wu J, Shi S, Zhang Y, Wu L, Liu Y, Liu C and Lei M. Telomeric TERB1-TRF1 interaction is crucial for male meiosis. Nat Struct Mol Biol. 2017 Dec;24(12):1073-1080.
    17. Yao C, Yuan Q, Niu M, Fu H, Zhou F, Zhang W, Wang H, Wen L, Wu L, Li Z, He Z. Distinct Expression Profiles and Novel Targets of MicroRNAs in Human Spermatogonia, Pachytene Spermatocytes, and Round Spermatids between OA Patients and NOA Patients. Mol Ther Nucleic Acids. 2017 Dec 15;9:182-194.
    18. Chen X, Che D, Zhang P, Li X, Yuan Q, Liu TT, Guo J, Feng T, Wu L, Liao M, He Z, Zeng WX. Profiling of miRNAs in porcine germ cells during spermatogenesis. Reproduction. 2017 Dec;154(6):789-798..
    19. Gou LT, Kang J, Dai P, Wang X, Li F, Zhao S, Zhang M, Hua M, Lu Y, Zhu Y, Li Z, Chen H, Wu L, Li D, Fu X, Li J, Shi H, Liu M. Ubiquitination-Deficient Mutations in Human Piwi Cause Male Infertility by Impairing Histone-to-Protamine Exchange during Spermiogenesis. Cell. 2017 Jun 1;169(6):1090-1104.e13.
    20. Qiu Y, Xu Y, Zhang Y, Zhou H, Deng YQ, Li XF, Miao M, Zhang Q, Zhong B, Hu Y, Zhang FC, Wu L, Qin CF, Zhou X. Human Virus-Derived Small RNAs Can Confer Antiviral Immunity in Mammals. Immunity. 2017 Jun 20;46(6):992-1004.e5.  
    21. Du H#, Zhao Y#, He J, Zhang Y, Xi H, Liu M, Ma J* and Wu L*. YTHDF2 destabilizes m6A-containing RNA through direct recruitment of the CCR4-NOT deadenylase complex. Nat Commun. 2016 Aug 25;7:12626.
    22. Yang Q#, Lin J#, Liu M, Li R, Tian B, Zhang X, Xu B, Liu M, Zhang X, Li Y, Shi H*, Wu L*. Highly Sensitive Sequencing Reveals Dynamic Modifications and Activities of Small RNAs in Mouse Oocytes and Early Embryos. Sci Adv. 2016 Jun 10;2(6):e1501482
    23. Shang R, Zhang F, Xu B, Xi H, Zhang X, Wang W, and Wu L*. Ribozyme-enhanced single-stranded Ago2-processed interfering RNA triggers efficient gene silencing with fewer off-target effects. Nat Commun. 2015 Oct 12; 6:8430.
    24. Liu S, Zhang X, Shi C, Lin J, Chen G, Wu B, Wu L, Shi H, Yuan Y, Zhou W, Sun Z, Dong X, Wang J. Altered microRNAs expression profiling in cumulus cells from patients with polycystic ovary syndrome. J Transl Med. 2015; 13:238.
    25. Chen T, Hao Y, Zhang Y, Li M, Wang M, Han W, Wu Y, Lv Y, Hao J, Wang L, Li A, Yang Y, Jin K, Zhao X, Li Y, Ping X, Lai W, Wu L, Jiang G, Wang H, Sang L, Wang X, Yang Y, Zhou Q. m(6)A RNA methylation is regulated by microRNAs and promotes reprogramming to pluripotency. Cell Stem Cell. 2015; 16(3):289-301.
    26. Wu Y#, Zhou H#, Fan X#, Zhang Y#, Zhang M, Wang Y, Xie Z, Bai M, Yin Q, Liang D, Tang W, Liao J, Zhou C, Liu W, Zhu P, Guo H, Pan H, Wu C, Shi H, Wu L*, Tang F*, Li J*. Correction of a Genetic Disease by CRISPR-Cas9-Mediated Gene Editing in Mouse Spermatogonial Stem Cells. Cell research. (2015) 25 (1):67-79. (Sanofi-Cell Research outstanding research paper award)
    27. Zhao Y, Lin J, Xu B, Hu S, Zhang X, and Wu L*. MicroRNA-mediated repression of nonsense mRNAs. Elife. (2014) Aug 8;3:e03032.    
      Insight: “Stop the nonsense!”  Elife. (2014) 3:e04300
    28. Gou L, Dai P, Yang J, Xue Y, Hu Y, Zhou Y, Kang J, Wang X, Li H, Hua M, Zhao S, Hu S, Wu L, Shi H, Li Y, Fu X, Qu L, Wang E, Liu M. Pachytene piRNAs instruct massive mRNA elimination during late spermiogenesis. Cell research. 2014; 24: 680–700.
    29. Piao X, Zhang X, Wu L* and Belasco JG*. CCR4-NOT deadenylates mRNA associated with RNA-induced silencing complexes in human cells. Mol Cell Biol. 2010 Mar ;30(6): 1486-1494.
    30. Savas JN, Ma B, Deinhardt K, Culver BP, Restituito S, Wu L, Belasco JG, Chao MV, and Tanese N. A role for huntington disease protein in dendritic RNA granules. J Biol Chem. 2010; 285(17): 13142-13153.
    31. Wu L, Fan J, and Belasco JG. Importance of translation and nonnucleolytic ago proteins for on-target RNA interference. Curr Biol. 2008;18(17): 1327-1332.
    32. Wu L, and Belasco JG. Examining the influence of microRNAs on translation efficiency and on mRNA deadenylation and decay. Methods Enzymol. 2008;449: 373-393.
    33. Wu L, and Belasco JG. Let me count the ways: mechanisms of gene regulation by miRNAs and siRNAs. Mol Cell. 2008; 29(1): 1-7. (Invited Review)
    34. Bao L, Zhou M, Wu L, Lu L, Goldowitz D, Williams RW, and Cui Y. PolymiRTS Database: linking polymorphisms in microRNA target sites with complex traits. Nucleic Acids Res. 2007;35(Database issue): D51-54.
    35. Wu L, Fan J, and Belasco JG. MicroRNAs direct rapid deadenylation of mRNA. Proc Natl Acad Sci USA. 2006;103(11): 4034-4039. 

      Commentary: “MicroRNAs: new players in an old game.”, Proc Natl Acad Sci USA. 2006; 103(11):3951-2.
      Research Highlights: “Behind the scenes”  Nature Review Genetics, Nature Review Molecular Biology, 2006; 243:7.

    36. Wu L, and Belasco JG. Micro-RNA regulation of the mammalian lin-28 gene during neuronal differentiation of embryonal carcinoma cells. Mol Cell Biol. 2005;25(21): 9198-9208.
    37. Wu L, Fan J, Jiang L, Wang H, Song R, Zhang Q, Zhu H, Li N, Liu Z, and Xu Z. A specific cis-hairpin ribozyme facilitates infection of a TMV-based DNA vector in tobacco protoplasts. J Virol Methods. 2003; 111(2): 101-109.
    38. Wu L, Jiang L, Zhou Z, Fan J, Zhang Q, Zhu H, Han Q, and Xu Z. Expression of foot-and-mouth disease virus epitopes in tobacco by a tobacco mosaic virus-based vector. Vaccine. 2003;21(27): 4390-4398.
    获奖及荣誉:
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    研究组成员:
  • 合影