Shan Zha, MD, PhD

Academic Appointments

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

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.

Departments and Divisions

Department of Pediatrics
Division of Pediatric Hematology, Oncology, and Stem Cell Transplantation
Department of Pathology & Cell Biology

Centers / Institutes / Programs

Herbert Irving Comprehensive Cancer Center

NIH Grants

DNADOUBLE-STRAND BREAK REPAIR, CHROMOSOME TRANSLOCATIONS AND CANCER (Federal Gov)
Apr 1 2020 - Mar 25 2025
THE CATALYTIC AND NON-CATALYTIC FUNCTIONS OF PARP1 IN CANCER BIOLOGY (Federal Gov)
Apr 1 2018 - Mar 31 2023
THESTRUCTURAL FUNCTION OF ATR IN DEVELOPMENT, ONCOGENESIS AND CANCER THERAPY (Federal Gov)
Apr 1 2017 - Mar 31 2022
THE ROLE OF ATM IN SUPPRESSION OF LYMOPHOMAS (Federal Gov)
Feb 1 2017 - Jan 31 2022
THESTRUCTURAL FUNCTION OF ATR IN DEVELOPMENT, ONCOGENESIS AND CANCER THERAPY (Federal Gov)
Jul 1 2018 - Jun 30 2021
DNA-PKCS PHOSPHORYLATION IN DNA REPAIR AND CHROMOSOMAL TRANSLOCATIONS (Federal Gov)
Dec 1 2014 - Nov 30 2020
DNA DOUBLE-STRAND BREAK REPAIR, CHROMOSOMES TRANSLOCATIONS AND CANCER (Federal Gov)
Apr 1 2014 - Mar 31 2020
DNA-PKCS PHOSPHORYLATION IN DNA REPAIR AND CHROMOSOMAL TRANSLOCATIONS (Federal Gov)
Dec 1 2014 - Nov 30 2019
DNA-PKCS PHOSPHORYLATION IN DNA REPAIR AND CHROMOSOMAL TRANSLOCATIONS (Federal Gov)
Dec 1 2014 - Nov 30 2019
CANCER CENTER SUPPORT GRANT (Federal Gov)
Jul 1 2014 - Jun 30 2019
CANCER CENTER SUPPORT GRANT (Federal Gov)
Jul 1 2014 - Jun 30 2019
DNA DOUBLE-STRAND BREAD REPAIR, CHROMOSOME TRANSLOCATIONS AND CANCER (Federal Gov)
Apr 1 2014 - Mar 31 2019
DNA DOUBLE-STRAND BREAD REPAIR, CHROMOSOME TRANSLOCATIONS AND CANCER (Federal Gov)
Apr 1 2014 - Mar 31 2019
ATM KINASES AS A TUMOR SUPPRESSOR IN DEVELOPING B CELLS (Private)
Jul 1 2013 - Jun 30 2018
NON-CATALYTIC FUNCTIONS OF DNA-PK IN DNA REPAIR AND TUMORIGENESIS (Federal Gov)
Sep 1 2014 - Aug 31 2017
NON-CATALYTIC FUNCTIONS OF DNA-PK IN DNA REPAIR AND TUMORIGENESIS (Federal Gov)
Sep 1 2014 - Aug 31 2017
THE STRUCTURAL FUNCTION OF ART IN DNA REPLICATION AND TUMORIGENESIS (Private)
Aug 1 2016 - Jul 31 2017
THE ROLE OF ATM IN SUPPRESSION OF LYMPHOMAS (Federal Gov)
Feb 1 2011 - Jan 31 2017
THE KINASE VS STRUCTURE FUNCTION OF ATM IN DNA REPAIR AND TUMOR SUPPRESSION (Private)
Jan 1 2013 - Dec 31 2016
ROLES OF XLF AND 53P1 IN DNA REPAIR AND SUPPRESSION OF LYMPHOMA (Private)
Jul 1 2013 - Jun 30 2016
TARGET ATM MUTATION FOR CANCER THERAPY (Private)
Jan 1 2014 - Dec 31 2015
THE ROLE OF XLF IN HEMATOPOIETIC STEM CELL MAINTENANCE AND FUNCTION (Federal Gov)
Aug 15 2013 - Jul 31 2015
THE ROLE OF XLF IN HEMATOPOIETIC STEM CELL MAINTENANCE AND FUNCTION (Federal Gov)
Aug 15 2013 - Jul 31 2015
THE ROLE OF ATM KINASE IN SUPPRESSION B CELL LYMPHOMAS (Private)
Jan 1 2012 - Dec 31 2014
THE ROLE OF ATM KINASE ACTIVITY IN THE DEVELOPMENT OF LYMPHOID MALIGNANCY (Private)
Jul 1 2012 - Jun 30 2014
THE MECHANISM OF CLONAL TRANSLOCATIONS IN PEDIATRIC T-ALL: THE ROLE OF ATM (Private)
Jul 1 2010 - Jun 30 2013
THE FUNCTION OF CERNUNNOS IN LYMPHOCYTE DEVELOPMENT AND LYMP HOMAGENESIS (Private)
Dec 1 2009 - Jun 30 2010

Publications

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
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
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
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
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
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
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
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
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
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
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
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
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