人才队伍

情况简介
院士风采
杰出青年
全所PI名录
 
 
地址:上海市岳阳路320号
邮编:200031
电话:86-21-54920000
传真:86-21-54921011
邮箱:sibcb@sibcb.ac.cn

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


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,“百人计划”入选者。


研究方向

非编码RNA分子机器的功能、机制及其应用


研究工作

        人类基因组中98%是非编码序列,编码蛋白质的序列仅占2%。非编码序列是生物进化过程中基因组中变化最大的部分,大量非编码序列被转录加工生成小RNA(如miRNA,siRNA和piRNA)和长非编码RNA(lncRNA),在表观遗传、转录和转录后等多个水平上控制基因的表达,是细胞内调控网络的重要组成部分,并与多种人类疾病存在密切关联。非编码RNA通常结合蛋白质形成RNA分子机器行使其功能,揭示这些非编码RNA分子机器的功能、机制及其在物种进化中的意义,是后基因组时代生命科学领域最重大的挑战之一。我们实验室主要运用生物化学和分子生物学手段,发展新的深度测序和生物信息学方法,从分子水平和RNA组学水平上研究非编码RNA的功能和分子机制。同时,我们还对非编码RNA分子机器进行改造,创建操控靶基因的新技术,为基础研究和疾病治疗提供有力工具。
 
        主要研究包括:
(1) RNA分子机器在肿瘤、精子和卵子发生、发育中调控基因表达的功能及其分子机制。
(2) 改造miRNA/RNAi和CRISPR等RNA分子机器,减少脱靶,提高效率。
(3) 研发新的高通量测序和生信分析方法及其在疾病诊疗中的应用。
 


代表性论文

发表论文 (*通讯作者)

  1. 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 Discovery. 2019 Feb 19. Doi: 10.1038/s41421-019-0087-9.[accepted]
  2. 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 Jan 31. doi: 10.1093/nar/gkz049. [Epub ahead of print]
  3. 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 Jan 14. doi: 10.1093/molbev/msz001. [Epub ahead of print]
  4. 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. doi: 10.1093/humrep/dey344
  5. 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. doi: 10.1038/s41594-018-0136-3.
  6. PMID: 30576496 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.
  7. 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.
  8. 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.
  9. 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..
  10. 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.
  11. 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.
  12. 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) 7:12626.DOI: 10.1038/ncomms12626
  13. 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) Vol. 2, no. 6, e1501482 DOI: 10.1126/sciadv.1501482
  14. 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. DOI: 10.1038/ncomms9430
  15. 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. doi: 10.1186/s12967-015-0605-y.
  16. 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.
  17. 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. 
  18. 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
  19. 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.
  20. 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) 30(6): 1486-1494.
  21. 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.
  22. 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.
  23. 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.
  24. 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)
  25. 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.
  26. Wu L, Fan J, and Belasco JG. MicroRNAs direct rapid deadenylation of mRNA. Proc Natl Acad Sci U S A. (2006) 103(11): 4034-4039. Commentary: “MicroRNAs: new players in an old game.”, PNAS. (2006) 103(11):3951-2.Research Highlights: “Behind the scenes”  Nature Review Genetics, Nature Review Molecular Biology, (2006) 243(7).
  27. 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.
  28. 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.
  29. 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(27-30): 4390-4398.

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