Bioinformatics and Genome Instability

DNA is the template for DNA replication and RNA transcription, making the maintenance of genome integrity extremely important. The Wu laboratory focuses on understanding mechanisms of genome instability in physiological and pathological processes. By developing bioinformatic approaches and sequencing techniques to probe repair associated DNA synthesis (SAR-seq) and DNA breaks (ENDseq), we aim to explore:

  • Association between chemotherapy induced neurological toxicity and endogenous DNA repair synthesis in neurons;
  • Roles of unstable repetitive sequences in tumor initiation and progression;
  • DNA break associated bioinformatic method development.
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    Project

    Research Summary

    Endogenous Single Strand Breaks in Neurons

    By developing two novel sequencing-based approaches to map single strand breaks (SSBs) and repair synthesis in post-mitotic neurons, we discovered that neuronal enhancers are hotspots of endogenous SSBs and are repaired by both short- and long-patch base excision repair. Furthermore, the SSBs are associated with TET-mediated active DNA demethylation. (Wu, W. et al. Nature, 2021;Wang, D.*,Wu, W*,Callen,E*. et al. Science, 2022).

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    Meiotic Double Strand Break processing

    By utilizing genome-wide DNA double strand break detection assay ENDseq, we have directly probed murine meiotic double strand breaks and end resection. Also, we demonstrated the roles of multiple key regulatory factors in meiotic DSB processing such as ATM, DMC1, PRDM9, and identified a novel SPO11-bound recombination intermediate. (Paiano, J.*, Wu, W.*, et al. Nature communications, 2020).

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    Fragile Simple Repeats

    Repetitive sequence is a major source of DNA damage. They usually are unstable and can form various secondary structures in vivo, including G4 quadruplex, triplex-DNA, cruciform, especially in the absence of mismatch repair. By applying ENDseq and its variants, we have discovered several types of fragile repeats in replication and cancers. (Matos-Rodrigues, G., et al. Molecular Cell, 2022; van Wietmarschen, N., et al Nature, 2020; Tubbs, A., et al. Cell, 2018)

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    About the PI

    Wei Wu

    Principal Investigator, Center for Excellence in Molecular Cell Science, CAS

    Dr. Wu received her B.E. in bioinformatics from Huazhong University of Science and Technology in 2012 and obtained her Ph.D. from the institute of biophysics of the Chinese Academy of Sciences in 2017, where she studied long non-coding RNA in cancer and noncoding RNA associated database development at the laboratory of Prof. Runsheng Chen. As a postdoctoral fellow in the laboratory of Dr. André Nussenzweig at the National Cancer Institute, she focused on studying mechanisms of DNA damage and repair by utilizing various novel sequencing technologies and bioinformatics analysis. She has received many awards during her training, including Fellows Award for Research Excellence, NCI Director’s Innovation Award, etc.

    Lab members

    Meet Our Team

    Zheng, Qijie

    Lab manager

    Wu, Shuheng

    Postdoc

    Hong, Rongjian

    Postdoc

    Yang, Jiajie

    Graduate student

    Song, Yawei

    Graduate student

    Liang, Yu

    Graduate student

    Yuan, Qingqing

    Graduate student

    Mei, Zilv

    Graduate student

    Gao, Jiaqi

    Graduate student

    Chen, Fangyi

    Intern

    Alumni

    Hanyu Bai, University of Toronto, Intern, 2023.6-2023.8

    Wenhan Zhou, University of Birmingham, Intern, 2023.6-2023.8

    Xiaopeng Wu, Tsinghua university, Intern, 2023.2-2023.6

    Publications

    Selected Publications

    * Equal contribution; # Corresponding author

    LncRNA INHEG promotes glioma stem cell maintenance and tumorigenicity through regulating rRNA 2’-O-methylation

    Lihui Liu*, Ziyang Liu*, Qinghua Liu*, Wei Wu*, Peng Lin*, Xing Liu*, Yuechuan Zhang, Dongpeng Wang, Briana C Prager, Ryan C Gimple, Jichuan Yu, Weixi Zhao, Qiulian Wu, Wei Zhang, Erzhong Wu, Xiaomin Chen, Jianjun Luo, Jeremy N Rich#, Qi Xie#, TaoJiang#, Runsheng Chen#.

    Nature Communications.14(1),7526, 2023.

    DNA Damage Atlas: an atlas of DNA damage and repair.

    Yu Liang*, Qingqing Yuan*, Qijie Zheng, Zilv Mei, Yawei Song, Huan Yan, Jiajie Yang, Shuheng Wu, Jiao Yuan#, Wei Wu#.

    Nucleic Acids Research, 2023, gkad845

    Active DNA demethylation promotes cell fate specification and the DNA damage response.

    Dongpeng Wang*, Wei Wu*#, Elsa Callen*, Raphael Pavani, Nicholas Zolnerowich, Srikanth Kodali, Dali Zong, Nancy Wong, Santiago Noriega, William J. Nathan, Gabriel Matos-Rodrigues, Raj Chari, Michael J. Kruhlak, Ferenc Livak, Michael Ward, Keith Caldecott, Bruno Di Stefano, André Nussenzweig#.

    Science. 378(6623):983-989, 2022.

    Neuronal enhancers are hotspots for DNA single-strand break repair.

    Wei Wu*, Sarah E Hill*, William J Nathan*, Jacob Paiano, Elsa Callen, Dongpeng Wang, Kenta Shinoda, Niek van Wietmarschen, Jennifer M Colón-Mercado, Dali Zong, Raffaella De Pace, Han-Yu Shih, Steve Coon, Maia Parsadanian, Raphael Pavani, Hana Hanzlikova, Solji Park, Seol Kyoung Jung, Peter J McHugh, Andres Canela, Chongyi Chen, Rafael Casellas, Keith W Caldecott#, Michael E Ward#, André Nussenzweig#.

    Nature. 593(7859):440-4, 2021.

    Repeat expansions confer WRN dependence in microsatellite-unstable cancers.

    Niek van Wietmarschen*, Sriram Sridharan*, William J Nathan*, Anthony Tubbs*, Edmond M Chan*, Elsa Callen, Wei Wu,, Frida Belinky, Veenu Tripathi, Nancy Wong, Kyla Foster, Javad Noorbakhsh, Kiran Garimella, Abimael Cruz-Migoni, Joshua A Sommers, Yongqing Huang, Ashir A Borah, Jonathan T Smith, Jeremie Kalfon, Nikolas Kesten, Kasper Fugger, Robert L Walker, Egor Dolzhenko, Michael A Eberle, Bruce E Hayward, Karen Usdin, Catherine H Freudenreich, Robert M Brosh, Stephen C West, Peter J McHugh, Paul S Meltzer, Adam J Bass, André Nussenzweig#

    Nature. 586 (7828), 292-298, 2020.

    ATM and PRDM9 regulate SPO11-bound recombination intermediates during meiosis.

    Jacob Paiano*, Wei Wu*, Shintaro Yamada, Nicholas Sciascia, Elsa Callen, Ana Paola Cotrim, Rajashree A Deshpande, Yaakov Maman, Amanda Day, Tanya T Paull, André Nussenzweig#

    Nature communications. 12;11(1):1-5, 2020.

    Dual roles of poly (dA: dT) tracts in replication initiation and fork collapse.

    Anthony Tubbs*, Sriram Sridharan*, Niek van Wietmarschen, Yaakov Maman, Elsa Callen, Andre Stanlie, Wei Wu, Xia Wu, Amanda Day, Nancy Wong, Mianmian Yin, Andres Canela, Haiqing Fu, Christophe Redon, Steven C Pruitt, Yan Jaszczyszyn, Mirit I Aladjem, Peter D Aplan, Olivier Hyrien, André Nussenzweig#

    Cell. 174 (5), 1127-1142. e19, 2018.

    Role of remodeling and spacing factor 1 in histone H2A ubiquitination-mediated gene silencing.

    Zhuo Zhang*, Amanda E Jones*, Wei Wu*, Jinman Kim, Yue Kang, Xiaobao Bi, Yue Gu, Ivan K Popov, Matthew B Renfrow, Marina N Vassylyeva, Dmitry G Vassylyev, Keith E Giles, Dongquan Chen, Ashwath Kumar, Yuhong Fan, Yufeng Tong, Chuan-Fa Liu, Woojin An, Chenbei Chang, Jianjun Luo#, Louise T Chow#, Hengbin Wang#

    Proceedings of the National Academy of Sciences. 114 (38), E7949-E7958, 2017.

    Oncogene. 36 (49), 6774-6783, 2017.

    NPInter v3. 0: an upgraded database of noncoding RNA-associated interactions.

    Yajing Hao*, Wei Wu*, Hui Li, Jiao Yuan, Jianjun Luo, Yi Zhao#, Runsheng Chen#

    Database. 2016

    Jiao Yuan*, Wei Wu*, Chaoyong Xie, Guoguang Zhao, Yi Zhao#, Runsheng Chen#

    Nucleic acids research. 42 (D1), D104-D108, 2014.

    Resources

    Computational tools

    DNA Damage Atlas (DDA) is an open access and comprehensive database that collects all publicly available datasets generated by genomic technologies probing for DNA damage and repair intermediates.

    NPInter is a database that collects interactions between noncoding RNAs and biomolecules.

    News

    2023 Nov, Wei's collabration work about functions of the lncRNA INHEG in Glioma is online in Nature Communications!

    2023 Sep, the first paper in Wu lab has been accepted in Nucleic Acids Research! Big congrats to Yu and Qingqing!

    2023 Aug, Welcome our new intern student Jiaqi!

    2023 Jun, Welcome our new intern student Wenhan and Hanyu!

    2023 May, Welcome our new intern student Zilv Mei!

    2023 Feb, Welcome our new intern student Xiaopeng Wu!

    2023 Jan, Qingqing joined us as a intern student. Welcome Qingqing!

    2022 Oct, Wei's collaboration paper(with Wang, D., and Callen, E. and Nussenzweig, A.) is accepted in Science! Congrats Wei!

    2022 Aug, Welcome our first postdoc, Shuheng!

    2022 Aug, Jiajie, Yawei and Yu joined as graduate students. Welcome!

    2022 Aug, Welcome our lab manager Qijie Zheng!

    2022 Aug, The collaboration paper (with Matos-Rodrigues, G., van Wietmarschen, N. and Nussenzweig, A.) on triplex DNA detection by S1-ENDseq is accepted in Molecular Cell.

    2022 Aug, Wei gave a virtual talk at Shangdong university.

    2022 July, Wei gave a talk at HMS-CSSA Frontiers Symposium.

    2022 May, We started hiring!

    Contact

    Join US!

    We are looking for passionate researchers of all stages (graduate students and postdocs to develop together. Please do not hesitate to contact me (wuw@sibcb.ac.cn) directly if you are interested in bioinformatics or DNA damage and repair.

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