研究团队
吴立刚
研究员
邮箱:  lgwu@@sibcb.ac.cn
电话:  54921321
他/她的实验室

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

研究内容:
        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,结合先进的高通量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。目前我们以癌症和精子发生为主要研究系统,研究包括:
(1) 非编码RNA在癌症和精子发生中的新功能。
(2) RNA分子机器调控基因表达的分子机制。
(3) 改造miRNA/RNAi和CRISPR分子机器,减少脱靶,提高效率。
(4) RNA分子机器在高通量筛选和疾病治疗中的应用。

发表论文 (*Corresponding author):
1. 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) 6:8430. DOI: 10.1038/ncomms9430
2. 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.
3. 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.
4. 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. 
5. 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
6. 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.
7. 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.
8. 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.
9. 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.
10. 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.
11. 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)
12. 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.
13. 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).
14. 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.
15. 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.
16. 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.
 

研究组成员
上海市浦东新区海科路333号,
电话:021-2077 8500
Email: ncpss@sibcb-ncpss.org