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首頁(yè) 全所PI名錄
  • 吳薇
  • 研究員，研究組長(zhǎng)，博士生導(dǎo)師
  • E-mail: wuw@sibcb.ac.cn
  • 實(shí)驗(yàn)室主頁(yè): https://wulab.sibcb.ac.cn/
    個(gè)人簡(jiǎn)介：

  • 　2012年畢業(yè)于華中科技大學(xué)，獲生物信息技術(shù)學(xué)士學(xué)位;2017年畢業(yè)于中科院生物物理研究所，獲生物信息學(xué)博士學(xué)位;2018至2022年于美國(guó)國(guó)家癌癥研究中心從事博士后研究;于2022年7月起任中科院分子細(xì)胞科學(xué)卓越創(chuàng)新中心(生物化學(xué)與細(xì)胞生物學(xué)研究所)研究員，研究組長(zhǎng)，博士生導(dǎo)師

    社會(huì)任職：
    研究方向：
  • 生物信息學(xué)、DNA損傷與修復(fù)
    研究工作：

  • 　　基因組DNA生物遺傳信息的重要載體，維持其穩(wěn)定性和準(zhǔn)確性是一切生命活動(dòng)的基礎(chǔ)。除UV射線等外源性刺激之外，細(xì)胞在正常生命代謝活動(dòng)中會(huì)發(fā)生內(nèi)源的程序性DNA損傷，包括起始減數(shù)分裂同源重組所需的DNA雙鏈斷裂;TET家族蛋白介導(dǎo)的主動(dòng)去甲基化過(guò)程所需的DNA單鏈斷裂;適應(yīng)性免疫中起始基因重排、高頻突變、DNA重組等過(guò)程以產(chǎn)生抗體多樣性的DNA損傷等。程序性損傷通常受到細(xì)胞精密地調(diào)控以保證遺傳信息的完整。然而，如果這些損傷在修復(fù)過(guò)程中發(fā)生錯(cuò)誤，例如DNA雙鏈斷裂的一端錯(cuò)誤地連接到不同染色體斷裂的另一端時(shí)會(huì)導(dǎo)致易位，則可能促進(jìn)癌癥等疾病的發(fā)生和影響疾病治療效果。

    　　與此同時(shí)，細(xì)胞內(nèi)也存在著大量?jī)?nèi)源的非程序性損傷，例如DNA復(fù)制過(guò)程中產(chǎn)生的堿基錯(cuò)配，核苷酸的氧化、烷化、脫氨基化這些異常修飾等?；蚪M上大量遍布的短串聯(lián)重復(fù)序列(Short Tandem Repeat, STR)也是一個(gè)非常重要的非程序損傷來(lái)源。STR由1-6個(gè)核苷酸通過(guò)重復(fù)排列組成。根據(jù)重復(fù)序列的不同，STR可以在RNA轉(zhuǎn)錄和DNA復(fù)制等過(guò)程中形成G四聯(lián)體(G-quadruplex)、三鏈DNA(Triplex DNA)、十字架(cruciform)等二級(jí)結(jié)構(gòu)，而這些結(jié)構(gòu)極易引起基因組不穩(wěn)定。

    　　我們將利用已開(kāi)發(fā)的用于檢測(cè)DNA斷裂和修復(fù)過(guò)程的高通量測(cè)序技術(shù)，結(jié)合生物信息學(xué)分析方法及分子生物學(xué)等多學(xué)科技術(shù)手段研究不同類(lèi)型內(nèi)源性損傷在腫瘤中的影響，包括(但不限于)以下幾個(gè)方向：1)神經(jīng)細(xì)胞內(nèi)的程序性DNA損傷與化療引起的神經(jīng)損傷之間的關(guān)聯(lián)。2)短重復(fù)序列引起的基因組不穩(wěn)定對(duì)腫瘤發(fā)生、進(jìn)展的影響。

    承擔(dān)科研項(xiàng)目情況：
    代表論著：
    1. Pavani, R.*, Tripathi, V.*, …, Wu, W., Cejka, P., Walter, J. C., & Nussenzweig, A. (2024). Structure and repair of replication-coupled DNA breaks. Science (New York, N.Y.), eado3867. Advance online publication.
    2. Liang, Y.*, Yuan, Q.*, Zheng, Q., Mei, Z., Song, Y., Yan, H., Yang, J., Wu, S., Yuan, J., & Wu, W. (2024). DNA Damage Atlas: an atlas of DNA damage and repair. Nucleic acids research, 52(D1), D1218–D1226. https://doi.org/10.1093/nar/gkad845
    3. Liu, L. *, Liu, Z. *, Liu, Q. *, Wu, W.*, …, Chen, R. (2023). LncRNA INHEG promotes glioma stem cell maintenance and tumorigenicity through regulating rRNA 2'-O-methylation. Nature communications, 14(1), 7526.
    4. Wang, D.*,?Wu, W.*, Callen, E.*, ..., Nussenzweig, A. (2022). Active DNA demethylation promotes cell fate specification and the DNA damage response.?Science?(New York, N.Y.),?378(6623), 983–989.
      • Perspectives by Isaac F. López-moyado and Anjana Rao,?Science. 2022 Dec 2;378(6623):948-949
    5. Matos-Rodrigues, G.*, van Wietmarschen, N.*,?Wu, W., …, Nussenzweig, A. (2022). S1-END-seq reveals DNA secondary structures in human cells.?Molecular cell,?82(19), 3538–3552.e5.
    6. Fowler, F., Chen, B. R., Zolnerowich, N.,?Wu, W.,?..., Tyler J.K. (2022). DNA-PK promotes DNA end resection at DNA double strand breaks in G0 cells.?Elife,?11, e74700.
    7. Paiano, J.*, Zolnerowich, N.*,?Wu, W., Pavani, R., …, Nussenzweig, A. (2021) Role of 53BP1 in End Protection and DNA synthesis at DNA breaks.?Genes & Development.?35:1-12
    8. Chen, B. R., Wang, Y., Tubbs, A., Zong, D., Fowler, F., Zolnerowich, N.,?Wu, W.,?..., Sleckman, B. P. (2021) Lin37-DREAM Prevents DNA End Resection and Homologous Recombination at DNA Double Strand Breaks in Quiescent Cells.?Elife,?10, e68466.
    9. Olbrich, T., Vega-Sendino, M., Tillo, D., Wu, W.,?..., Macias, S. R. (2021). CTCF is a Barrier for Totipotent-like Reprogramming.?Nature Communications, 12(1), 4856.
    10. Wu, W.*,Hill, S. E.*, Nathan, W.*, ..., Nussenzweig, A. (2021). Neuronal enhancers are hotspots for DNA single-strand break repair.?Nature,593(7859), 440-444.
      • Spotlighted by Vishnu Dileep and Li-Huei Tsai,?Neuron, 2021,109(11), 1766-1768
      • Research Highlight by?Nature Reviews Molecular Cell Biology, 2021,22(5), 304-305.
    11. Shinoda, K., Zong, D., Callen, E.,?Wu, W.,Dumitrache, L. C., Belinky, F., ..., Nussenzweig, A. (2021). The dystonia gene THAP1 controls DNA double-strand break repair choice.Molecular Cell,?81(12), 2611-2624.
    12. van Wietmarschen, N.*, Sridharan, S.*, Nathan, W.J.*, Tubbs, A.*, Chan, E.M.*, Callen, E.#,?Wu, W.#(#equal contribution),…, Nussenzweig, A. (2020). Repeat expansions confer WRN dependence in microsatellite-unstable cancers.?Nature, 586(7828), 292-298.
    13. Nacson, J., Di Marcantonio, D., Wang, Y., Bernhardy, A.J., Clausen, E., Hua, X., Cai, K.Q., Martinez, E., Feng, W., Callén, E.,?Wu, W.,?…, Johnson, N. (2020). BRCA1 Mutational Complementation Induces Synthetic Viability.?Molecular Cell, 78(5), 951-959.
    14. Mahgoub, M.*, Paiano, J.*, Bruno, M.,?Wu, W.,?…, Macfarlan, T.S. (2020). Dual histone methyl reader ZCWPW1 facilitates repair of meiotic double strand breaks in male mice.?Elife, 9, e53360.
    15. Sciascia, N.,?Wu, W.#,?Zong, D.#(#equal contribution),…, Nussenzweig, A. (2020). Suppressing Proteasome Mediated Processing of Topoisomerase II DNA-Protein Complexes Preserves Genome Integrity.?Elife, 9, e53447.
    16. Paiano, J.*,?Wu, W.*,?…, Nussenzweig, A. (2020). ATM and PRDM9 Regulate SPO11-bound Recombination Intermediates During Meiosis.?Nature Communications,11(1), 1-15.
    17. Callen, E.*, Zong, D.*,?Wu, W., …, Nussenzweig, A. (2019). 53BP1 Enforces Distinct Pre- and Post-resection Blocks on Homologous Recombination.?Molecule Cell, 77(1), 26-38.
    18. Wang, Y.*, Zhu, P.*, Luo, J.*, Wang, J.*, Liu, Z.*,?Wu, W., …, Fan, Z. (2019). LncRNA HAND2-AS1 promotes liver cancer stem cell self-renewal via BMP signaling.?The EMBO journal, 38(17), e101110.
    19. Tubbs, A.*, Sridharan, S.*, van Wietmarschen, N., Maman, Y., Callen, E., Stanlie, A.,?Wu, W., …, Nussenzweig, A. (2018). Dual roles of Poly (dA: dT) tracts in replication initiation and fork collapse.?Cell, 174(5), 1127-1142.
    20. Ye, B. *, Liu, B. *, Yang, L. *, Zhu, X. *, Zhang, D.*,?Wu, W., …, Fan, Z. (2018). LncKdm2b controls self-renewal of embryonic stem cells via activating expression of transcription factor Zbtb3.?The EMBO journal, 37(8), e97174.
    21. Cui, Y.*, Chen, X.*, Niu, Y. *, Wang, D., Luo, H., Fan. Z., Wang, D.,?Wu, W., ... Chen, R. (2017). Dynamic-BM: Multi-species dynamic BodyMap database from temporal RNA-seq data.?Briefings in Bioinformatics, 19(6), 1302-1309.
    22. Zhang, Z.*, Jones, A E.*,?Wu, W.*, Kim, J., Kang, Y., Bi, X., ..., Wang, H. (2017). Role of remodeling and spacing factor 1 in histone H2A ubiquitination-mediated gene silencing.?Proc Natl Acad Sci U S A, 114(38), E7949-E7958.
    23. Sun, Y.*, Wei, G.*, Luo, H.*,?Wu, W.*, Skogerb？, G., Luo, J. & Chen, R. (2017). The Long Noncoding RNA SNHG1 Regulates Both Local and Distal Genes in Cancer.?Oncogene, 36(49), 6774-6783.
    24. Yan, X.*, Zhang, D.*,?Wu, W.,?…, Fan, Z. (2017). Mesenchymal stem cells promote hepatocarcinogenesis via lncRNA-MUF interaction with ANXA2 and miR-34a.?Cancer research, 77(23), 6704-6716.
    25. Chen, J., Liu, L., Wei, G.,Wu, W., Luo, H., Yuan, J., ... Chen, R. (2016). The long noncoding RNA ASNR regulates degradation of Bcl-2 mRNA through its interaction with AUF1.?Scientific reports, 6(1), 1-11.
    26. Hao, Y.*,Wu, W.*, Li, H., Yuan, J., Luo, J., Zhao, Y.?& Chen, R. (2016). NPInter v3.0: an upgraded database of noncoding RNA-associated interactions.Database, 2016.
    27. Yuan, J.*, Yue, H.*, Zhang, M., Luo, J., Liu, L.,?Wu, W., ..., Chen, R. (2016). Transcriptional profiling analysis and functional prediction of long noncoding RNAs in cancer.?Oncotarget, 7(7), 8131.
    28. Zhao, Y.*, Li, H.*, Fang, S., Kang, Y.,?Wu, W., Hao, Y., ..., Chen, R. (2016). NONCODE 2016: an informative and valuable data source of long non-coding RNAs.?Nucleic Acids Res, 44(D1), D203-D208.
    29. Yuan, J.*,?Wu, W.*, Xie, C., Zhao, G., Zhao, Y. & Chen, R. (2014).NPInter v2.0: an updated database of ncRNA interactions.?Nucleic Acids Res, 42(D1), D104-D108.
    30. Xie, C.*, Yuan, J.*, Li, H., Li, M., Zhao, G., Bu, D., Zhu, W.,?Wu, W., ..., Chen, R. & Zhao, Y. (2014). NONCODEv4: exploring the world of long non-coding RNA genes.?Nucleic Acids Res, 42(D1), D98-D103.
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    研究組成員：