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首頁 全所PI名錄
  • 吳立剛
  • 研究員,研究組長,博士生導(dǎo)師
  • E-mail: lgwu@@sibcb.ac.cn
  • 實驗室主頁: https://wulg-lab.sibcb.ac.cn/LabIntroduction
    個人簡介:
  •   1996年畢業(yè)于上海交通大學(xué)生物科學(xué)與技術(shù)系,獲學(xué)士學(xué)位。2001年畢業(yè)于中國科學(xué)院上海植物生理研究所遺傳學(xué)專業(yè),獲博士學(xué)位。2001年至2008年在美國紐約大學(xué)(NYU)醫(yī)學(xué)院從事博士后研究。2008年10月起任中科院上海生科院生化與細(xì)胞所研究員。

    社會任職:
    研究方向:
  • 小RNA和mRNA的調(diào)控機(jī)制與藥物開發(fā)
    研究工作:
  •   研究mRNA和非編碼小RNA調(diào)控的分子機(jī)制、理性設(shè)計和轉(zhuǎn)化應(yīng)用。運用生物化學(xué)、分子生物學(xué)手段,結(jié)合高通量測序和生物信息學(xué)方法,從分子水平和RNA組學(xué)水平,研究mRNA和非編碼小RNA在細(xì)胞命運決定、生殖細(xì)胞生成過程中的生物學(xué)功能和分子機(jī)制;運用獲得的知識指導(dǎo)RNA分子機(jī)器的理性設(shè)計,開發(fā)新技術(shù)新方法,用于臨床疾病診治和工業(yè)化生產(chǎn)。

      研究內(nèi)容包括:

      (1)mRNA在細(xì)胞中的穩(wěn)定性調(diào)控的分子機(jī)制。

      (2)miRNA、siRNA、piRNA等非編碼小RNA的功能和機(jī)制。

     ?。?)mRNA和siRNA(RNAi)藥物和新療法的開發(fā)。

     ?。?)單細(xì)胞小RNA/mRNA高通量測序技術(shù)和生信算法的開發(fā)和應(yīng)用。

     ?。?)基因編輯復(fù)合物分子機(jī)器的改進(jìn)及應(yīng)用。

    承擔(dān)科研項目情況:
    代表論著:
    1. Chang Y#, Wu L*.CapHLA: a comprehensive tool to predict peptide presentation and binding to HLA class I and class II. Brief Bioinform. 2025; 26(1): bbae595.
    2. Li Y#, Sang Y#, Chang Y#, Xu C#, Lin Y, Zhang Y, Chiu PCN, Yeung WSB, 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;149(21):1670-1688.
    3. Hou L#, Liu W#, Zhang H, Li R, Liu M, Shi H, Wu L*. Divergent composition and transposon-silencing activity of small RNAs in mammalian oocytes. Genome Biol. 2024;25(1):80.
    4. Wang X#, Jiang Q#, Zhang H#, He Z, Song Y, Chen Y, Tang N, Zhou Y, Li Y, Antebi A, Wu L*, Han JJ*, Shen Y*. Tissue-specific profiling of age-dependent miRNAomic changes in Caenorhabditis elegans. Nat Commun.2024;15(1):955.
    5. 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.
    6. 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.
    7. 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.
    8. 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.
    9. 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.
    10. 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.
    11. 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.
    12. 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.
    13. 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.?
    14. 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.?
    15. 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.
    16. 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.
    17. 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
    18. 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.
    19. ?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.
    20. 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.
    21. 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.
    22. 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.
    23. 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.
    24. 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.
    25. 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.
    26. 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.
    27. 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..
    28. 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.
    29. 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. ?
    30. 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.
    31. 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.
    32. 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.
    33. 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.
    34. 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.
    35. 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)
    36. 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.
    37. 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.
    38. 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.
    39. 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.
    40. 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.
    41. Wu L, Belasco JG. Examining the influence of microRNAs on translation efficiency and on mRNA deadenylation and decay.?Methods Enzymol. 2008;449: 373-393.
    42. 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)
    43. 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.
    44. Wu L, Fan J, 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.
    45. 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.
    46. 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.
    47. 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.

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    獲獎及榮譽:
    研究組成員:
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