Shan Zha, MD, PhD

  • James A Wolff Professor of Pediatrics, Pathology and Cell Biology and of Microbiology and Immunology (in the Institute for Cancer Genetics and in the Herbert Irving Comprehensive Cancer Center)
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Overview

Academic Appointments

  • James A Wolff Professor of Pediatrics, Pathology and Cell Biology and of Microbiology and Immunology (in the Institute for Cancer Genetics and in the Herbert Irving Comprehensive Cancer Center)

Research

The Zha lab investigates how defects in DNA repair and DNA damage responses impact normal immune system development, lymphomagenesis, and treatment responses. The lab has developed cutting-edge technologies, including high-throughput translocation sequencing, sing cell-seq, multi-color flow-cytometry, CRISPR-based depletion and activation screens, high-content live-cell imaging, and a collection of over sixty-five unique mouse models, including the serial of mouse models expressing catalytically inactive ATM, ATR, DNA-PKcs, and now PARP1 and PARP2, which revealed unexpected structural function of DNA damage response factors. More details can be found at zhalab.org. We invite committed young scientists to join us in the adventures.

Selected Publications

  1. The cancer-associated ATM R3008H mutation reveals the link between ATM activation and its exchange
    Milanovic M, Houghton LM, Menolfi D, Lee JH, Yamamoto K, Li Y, Lee BJ, Xu J, Estes VM, Wang D, McKinnon PJ, Paull TT, Zha S
    Cancer Res. 2020.
    PMID: 33239428, DOI: 10.1158/0008-5472.CAN-20-2447
  2. Clinical PARP inhibitors do not abrogate PARP1 exchange at DNA damage sites in vivo
    Shao Z, Lee BJ, Rouleau-Turcotte É, Langelier MF, Lin X, Estes VM, Pascal JM, Zha S
    Nucleic Acids Res. 2020.
    PMID: 32890402, DOI: 10.1093/nar/gkaa718
  3. Dual-Color Plasmonic Nanosensor for Radiation Dosimetry
    Tao Y, Li M, Liu X, Leong KW, Gautier J, Zha S
    ACS Appl Mater Interfaces. 2020.
    PMID: 32337977, DOI: 10.1021/acsami.0c03001
  4. DNA-PKcs has KU-dependent function in rRNA processing and haematopoiesis
    Shao Z, Flynn RA, Crowe JL, Zhu Y, Liang J, Jiang W, Aryan F, Aoude P, Bertozzi CR, Estes VM, Lee BJ, Bhagat G, Zha S, Calo E
    Nature. 2020.
    PMID: 32103174, DOI: 10.1038/s41586-020-2041-2
  5. CtIP is essential for early B cell proliferation and development in mice
    Liu X, Wang XS, Lee BJ, Wu-Baer FK, Lin X, Shao Z, Estes VM, Gautier J, Baer R, Zha S
    J Exp Med. 2019.
    PMID: 31097467, DOI: 10.1084/jem.20181139
  6. Kinase-dead ATR differs from ATR loss by limiting the dynamic exchange of ATR and RPA
    Menolfi D, Jiang W, Lee BJ, Moiseeva T, Shao Z, Estes V, Frattini MG, Bakkenist CJ, Zha S
    Nat Commun. 2018.
    PMID: 30559436, DOI: 10.1038/s41467-018-07798-3
  7. Kinase-dependent structural role of DNA-PKcs during immunoglobulin class switch recombination
    Crowe JL, Shao Z, Wang XS, Wei PC, Jiang W, Lee BJ, Estes VM, Alt FW, Zha S
    Proc Natl Acad Sci USA. 2018.
    PMID: 30072430, DOI: 10.1073/pnas.1808490115
  8. PAXX promotes KU accumulation at DNA breaks and is essential for end-joining in XLF-deficient mice
    Liu X, Shao Z, Jiang W, Lee BJ, Zha S
    Nat Commun. 2017.
    PMID: 28051062, DOI: 10.1038/ncomms13816
  9. Kinase-dead ATM protein is highly oncogenic and can be preferentially targeted by Topo-isomerase I inhibitors
    Yamamoto K, Wang J, Sprinzen L, Xu J, Haddock CJ, Li C, Lee BJ, Loredan DG, Jiang W, Vindigni A, Wang D, Rabadan R, Zha S
    Elife. 2016.
    PMID: 27304073, DOI: 10.7554/eLife.14709
  10. Differential phosphorylation of DNA-PKcs regulates the interplay between end-processing and end-ligation during nonhomologous end-joining
    Jiang W, Crowe JL, Liu X, Nakajima S, Wang Y, Li C, Lee BJ, Dubois RL, Liu C, Yu X, Lan L, Zha S
    Mol Cell. 2015.
    PMID: 25818648, DOI: 10.1016/j.molcel.2015.02.024
  11. Kinase-dead ATM protein causes genomic instability and early embryonic lethality in mice
    Yamamoto K, Wang Y, Jiang W, Liu X, Dubois RL, Lin CS, Ludwig T, Bakkenist CJ, Zha S
    J Cell Biol. 2012.
    PMID: 22869596, DOI: 10.1083/jcb.201204098
  12. ATM damage response and XLF repair factor are functionally redundant in joining DNA breaks
    Zha S, Guo C, Boboila C, Oksenych V, Cheng HL, Zhang Y, Wesemann DR, Yuen G, Patel H, Goff PH, Dubois RL, Alt FW
    Nature. 2011.
    PMID: 21160472, DOI: 10.1038/nature09604
  13. Lymphocyte-specific compensation for XLF/cernunnos end-joining functions in V(D)J recombination
    Li G, Alt FW, Cheng HL, Brush JW, Goff PH, Murphy MM, Franco S, Zhang Y, Zha S
    Mol Cell. 2008.
    PMID: 18775323, DOI: 10.1016/j.molcel.2008.07.017