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: wulg-lab.sibcb.ac.cn
    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:
    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:
    代表论著:
    1. Li Y#, Sang Y#,Chang Y#, Xu C#, Lin Y, Zhang Y, Chiu P, Yeung W, Zhou H, Dong N, Xu L, Chen J, Zhao W, Liu L, Yu D, Zang X, Ye J, Yang J, Wu Q, Li D*, Wu L*, Du* M. A galectin-9 driven CD11chigh decidual macrophage subset suppresses uterine vascular remodeling in preeclampsia. Circulation. 2024 (In Press).
    2. Li Y#, Cao Y#, Liu W#, Chen F, Zhang H, Zhou H, Zhao A, Luo N, Liu J*, Wu L*. Candidate biomarkers of EV-microRNA in detecting REM sleep behavior disorder and Parkinson's disease. NPJ Parkinsons Dis. 2024;10(1):18.
    3. Lv X #, Xiao W#, Lai Y#, Zhang Z#, Zhang H#, Qiu C, Hou L, Chen Q, Wang D, Gao Y, Song Y, Shui X, Chen Q, Qin R, Liang S, Zeng W, Shi A*, Li J*, Wu L*. The non-redundant functions of PIWI family proteins in gametogenesis in golden hamsters. Nat Commun. 2023;14(1):5267.
    4. Li  Q#, Lu J#, Yin X #, Chang Y #, Wang C #, Yan M #, Feng L, Cheng Y , Gao Y, Xu B, Zhang Y, Wang Y, Cui G, Xu L, Sun Y, Zeng R, Li Y, Jing N, Xu G*, Wu L*, Tang F*, Li J*. Base editing-mediated one-step inactivation of the Dnmt gene family reveals critical roles of DNA methylation during mouse gastrulation. Nat Commun. 2023;14(1):2922.
    5. Zhang Y#, Liu W#, Zhang H#, Sun B, Chen T, Hu M, Zhou H, Cao Y, Han B*, Wu L*. Extracellular vesicle long RNA markers of early-stage lung adenocarcinoma.Int J Cancer. 2023; 152(7):1490-1500.
    6. Liu M #, Liu P#, Chang Y#, Xu B, Wang N, Qin L, Zheng J*, Liu Y*, Wu L*, Yan H*. Genome-wide DNA methylation profiles and small noncoding RNA signatures in sperm with a high DNA fragmentation index. J Assist Reprod Genet. 2022; 39(10):2255-2274.
    7. Zhou G, Gu Y, Zhu Z, Zhang H, Liu W, Xu B, Zhou F, Zhang M, Hua K*, Wu L*, 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. Front Med (Lausanne). 2022; 9:810761.
    8. 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 in Caenorhabditis elegans.The EMBO Journal. 2022; 41:e109633.
    9. 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. Nat Cell Biol. 2021; 23(9):1013-1022.
    10. 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; 22:900-909. 
    11. Zhu Z#, Zhang Y#, Wu L*, Hua K*, Ding J*, Regeneration-Related Functional Cargoes in Mesenchymal Stem Cell-Derived Small Extracellular Vesicles. Stem Cells Dev. 2020; 29(1):15-24. 
    12. 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, Wu L*. Single-cell CAS-seq reveals a class of short PIWI-interacting RNAs in human oocytes. Nat Commun. 2019; 10(1):3389.
    13. 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;11(5):408-420.
    14. Hua M#, Liu W#, Chen Y#, Zhang F, Xu B, Liu S, Chen G*, Shi H*, Wu L*. Identification of small non-coding RNAs as sperm quality biomarkers for in vitro fertilization. Cell Discov. 2019; 5:20
    15. Zhao Y#, Zhang Y#, Teng Y, Liu K, Liu Y, Li W, 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;47(6):e33.
    16. 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;36(4):663-678.
    17. 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;34(2):248-260.
    18. 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 X*. A novel class of microRNA-recognition elements that function only within open reading frames. Nat Struct Mol Biol. 2018; 25(11):1019-1027.
    19. 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;9(1):3875.
    20. 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; 293(26):9981-9994.
    21. Zhang Y, Liu W, Li R, Gu J, Wu P, Peng C, Ma J, Wu L, Yu Y, Huang Y. Structural insights into the sequencespecific recognition of Piwi by Drosophila Papi. Proc Natl Acad Sci. 2018; 115(13):3374-3379.
    22. 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; 24(12):1073-1080.
    23. 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; 9:182-194.
    24. 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;154(6):789-798..
    25. 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;169(6):1090-1104.e13.
    26. 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;46(6):992-1004.e5.  
    27. Du H#, Zhao Y#, He J, Zhang Y, Xi H, Liu M, Ma J*, Wu L*. YTHDF2 destabilizes m6A-containing RNA through direct recruitment of the CCR4-NOT deadenylase complex. Nat Commun. 2016; 7:12626.
    28. 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; 2(6):e1501482.
    29. Shang R, Zhang F, Xu B, Xi H, Zhang X, Wang W, Wu L*. Ribozyme-enhanced single-stranded Ago2-processed interfering RNA triggers efficient gene silencing with fewer off-target effects. Nat Commun. 2015; 6:8430.
    30. 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.
    31. 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.
    32. 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)
    33. Zhao Y, Lin J, Xu B, Hu S, Zhang X, Wu L. MicroRNA-mediated repression of nonsense mRNAs. Elife. (2014);3:e03032.    
          Insight: “Stop the nonsense!”  Elife. (2014) 3:e04300.
    34. 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.
    35. Piao X, Zhang X, Wu L*, Belasco JG*. CCR4-NOT deadenylates mRNA associated with RNA-induced silencing complexes in human cells. Mol Cell Biol. 2010; 30(6): 1486-1494.
    36. Savas JN, Ma B, Deinhardt K, Culver BP, Restituito S, Wu L, Belasco JG, Chao MV, Tanese N. A role for huntington disease protein in dendritic RNA granules. J Biol Chem. 2010; 285(17): 13142-13153.
    37. Wu L, Fan J, Belasco JG. Importance of translation and nonnucleolytic ago proteins for on-target RNA interference. Curr Biol. 2008;18(17): 1327-1332.
    38. Wu L, Belasco JG. Examining the influence of microRNAs on translation efficiency and on mRNA deadenylation and decay. Methods Enzymol. 2008;449: 373-393.
    39. Wu L, Belasco JG. Let me count the ways: mechanisms of gene regulation by miRNAs and siRNAs. Mol Cell. 2008; 29(1): 1-7. (Invited Review)
    40. Bao L, Zhou M, Wu L, Lu L, Goldowitz D, Williams RW, Cui Y. PolymiRTS Database: linking polymorphisms in microRNA target sites with complex traits. Nucleic Acids Res. 2007;35(Database issue): D51-54.
    41. Wu L, Fan J, Belasco JG. MicroRNAs direct rapid deadenylation of mRNA. Proc Natl Acad Sci USA. 2006;103(11): 4034-4039. 
    42. 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 MolecularBiology, 2006; 243:7.
    43. Wu L, 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.
    44. Wu L, Fan J, Jiang L, Wang H, Song R, Zhang Q, Zhu H, Li N, Liu Z, 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.
    45. Wu L, Jiang L, Zhou Z, Fan J, Zhang Q, Zhu H, Han Q, 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:
    研究组成员:
  • 合影