Zhiguo Zhang, PhD

Academic Appointments

  • Professor of Epigenomics and Molecular Biology (in Pediatrics, Genetics and Development and in the Institute of Cancer Genetics)
Zhiguo Zhang, PhD

Email: zz2401@cumc.columbia.edu

Zhiguo Zhang’s laboratory studies epigenetic inheritance and cancer epigenetics. How epigenetic states are transmitted into daughter cells is a challenging, but yet poorly understood, question in the chromatin and epigenetic fields. Recently, it became clear that epigenetic alterations contribute to tumorigenesis and development of drug. However, how alterations in epigenetic landscape contribute to tumorigenesis and drug resistance is largely unexplored. The laboratory focuses on three major directions to study epigenetic inheritance and cancer epigenetics. First, how parental histones, the primary carrier of epigenetic information, are reassembled into nucleosomes following DNA replication in yeast and mammalian cells. Second, how onco-histone mutations found in gliomas reprogram cancer epigenomes. Third, how epigenetic changes drive drug resistance in brain tumors. The overall goal is to elucidate the molecular mechanisms of epigenetic inheritance and drug resistance and discover novel therapeutics for cancer treatment in the future.

Departments and Divisions

  • Department of Pediatrics
    Division of Pediatric Hematology, Oncology, and Stem Cell Transplantation
  • Department of Genetics & Development

Lab Locations

  • Irving Cancer Research Center

    1130 St. Nicholas Avenue
    New York, NY 10032
    Phone:
    (212) 851-4936
    Lab Phone:
    (212) 851-4937
    Email:
    zz2401@cucm.columbia.edu

Past Positions

1988-1989 Research Technician, Dalian Institute of Chemical Physics, Chinese Academy of Science, Dalian, China

1998-2003 Postdoctoral Fellow, Cold Spring Harbor Lab, Cold Spring Harbor, NY

2003-2008 Assistant Professor, Department of Biochemistry and Molecular Biology, Mayo Clinic Rochester, Rochester, MN

2008-2012 Associate Professor, Department of Biochemistry and Molecular Biology, Mayo Clinic Rochester, Rochester, MN

2012-2016 Professor, Department of Biochemistry and Molecular Biology, Mayo Clinic Rochester, Rochester, MN

08,2016-present Professor of Pediatrics and Professor of Genetics and Development, Institute for Cancer Genetics, Columbia University

Committees / Societies / Memberships

1998-present American Association for the Advancement of Science

1998-present American Society for Biochemistry and Molecular Biology

2013-present Society for NeuroOncology

NIH Grants

  • MOLECULAR MECHANISMS UNDERLYING THE PREVENTION OF BCC RESISTANC (Federal Gov)

    Apr 7 2020 - Jan 31 2025

    THE EPIGENETIC MECHANISMS OF HIGH-GRADE PEDIA (Federal Gov)

    Jun 15 2017 - May 31 2022

    MECHANISTICS STUDOES ON THE WNT5A SIGNAL PATHWAY IN DIPG TUMOR (Private)

    Jan 2 2020 - Dec 31 2021

    MECHANISMS FOR HISTONE SEGREGATION AT DNA REPLICATION FORKS AND IMPLICATIONS FOR EPIGENETIC INHERITANCE (Federal Gov)

    Sep 17 2019 - Aug 31 2021

    MECHANISMS OF EPIGENETIC INHERITANCE (Federal Gov)

    Sep 1 2016 - Jul 31 2021

    MECHANISMS FOR HISTONE SEGREGATION AT DNA REPLICATIONFORKS AND IMPLICATIONS FOR EPIGENETIC INHERITANCE (Private)

    Jul 1 2019 - Jun 30 2021

    THE ROLE OF A HISTONE H4 PHOSPHORYLATION IN DRUG RESISTANCE (Federal Gov)

    Aug 1 2016 - Jul 31 2018

    HISTONE CHAPERONES AND TRANSCRIPTIONAL SILENCING (Federal Gov)

    Aug 1 2016 - Jul 31 2017

    IDENTIFY AND CHARACTERIZE GENES INVOLVED IN X-CHROMOSOME INACTIVATION (Federal Gov)

    Aug 1 2016 - Apr 30 2017

    REGULATION OF NUCLEOSOME ASSEMBLY (Federal Gov)

    Aug 1 2016 - Jan 31 2017

Lab Projects

  • 1) Determine how parental histone H3-H4 tetramers, which carry modifications for inheritance, are assembled into nucleosomes in yeast and mammalian cells

    2) Elucidate how chromatin regulators impact DNA synthesis of leading and lagging strands and how the stability of replication forks maintained under replication stress

    3) Understand histone mutations reprogram cancer epigenome and promote tumorigenesis of brain and bone tumors

    4) Determine how epigenetic changes promote drug resistance in brain tumors

Lab Members

  • Hui Zhou, Research Scientist
  • Albert Serra Cardona, Postdoctoral Fellow
  • Minjie Zhang, Postdoctoral Fellow
  • Xu Zhang, Postdoctoral Fellow
  • Xiaowei Xu, Postdoctoral Fellow
  • Yan Mo, Postdoctoral Fellow
  • Dong Fang, Research Scientist
  • Xinmin Zhang, visiting scientist
  • Haiyan Gan, Research Scientist

Publications

  1. DNA polymerase α interacts with H3-H4 and facilitates the transfer of parental histones to lagging strands
    Li Z, Hua X, Serra-Cardona A, Xu X, Gan S, Zhou H, Yang WS, Chen CL, Xu RM, Zhang Z
    Sci Adv. 2020.
    PMID: 32923642, DOI: 10.1126/sciadv.abb5820
  2. The Mcm2-Ctf4-Polα Axis Facilitates Parental Histone H3-H4 Transfer to Lagging Strands
    Gan H, Serra-Cardona A, Hua X, Zhou H, Labib K, Yu C, Zhang Z
    Mol Cell. 2018.
    PMID: 30244834, DOI: 10.1016/j.molcel.2018.09.001
  3. A mechanism for preventing asymmetric histone segregation onto replicating DNA strands
    Yu C, Gan H, Serra-Cardona A, Zhang L, Gan S, Sharma S, Johansson E, Chabes A, Xu RM, Zhang Z
    Science. 2018.
    PMID: 30115745, DOI: 10.1126/science.aat8849
  4. Multisite Substrate Recognition in Asf1-Dependent Acetylation of Histone H3 K56 by Rtt109
    Zhang L, Serra-Cardona A, Zhou H, Wang M, Yang N, Zhang Z, Xu RM
    Cell. 2018.
    PMID: 30057113, DOI: 10.1016/j.cell.2018.07.005
  5. A novel enhancer regulates MGMT expression and promotes temozolomide resistance in glioblastoma
    Chen X, Zhang M, Gan H, Wang H, Lee JH, Fang D, Kitange GJ, He L, Hu Z, Parney IF, Meyer FB, Giannini C, Sarkaria JN, Zhang Z
    Nat Commun. 2018.
    PMID: 30054476, DOI: 10.1038/s41467-018-05373-4
  6. Checkpoint Kinase Rad53 Couples Leading- and Lagging-Strand DNA Synthesis under Replication Stress
    Gan H, Yu C, Devbhandari S, Sharma S, Han J, Chabes A, Remus D, Zhang Z
    Mol Cell. 2017.
    PMID: 29033319, DOI: 10.1016/j.molcel.2017.09.018
  7. RPA Interacts with HIRA and Regulates H3.3 Deposition at Gene Regulatory Elements in Mammalian Cells
    Zhang H, Gan H, Wang Z, Lee JH, Zhou H, Ordog T, Wold MS, Ljungman M, Zhang Z
    Mol Cell. 2017.
    PMID: 28107649, DOI: 10.1016/j.molcel.2016.11.030
  8. The histone H3.3K36M mutation reprograms the epigenome of chondroblastomas
    Fang D, Gan H, Lee JH, Han J, Wang Z, Riester SM, Jin L, Chen J, Zhou H, Wang J, Zhang H, Yang N, Bradley EW, Ho TH, Rubin BP, Bridge JA, Thibodeau SN, Ordog T, Chen Y, van Wijnen AJ, Oliveira AM, Xu RM, Westendorf JJ, Zhang Z
    Science. 2016.
    PMID: 27229140, DOI: 10.1126/science.aae0065
  9. Strand-specific analysis shows protein binding at replication forks and PCNA unloading from lagging strands when forks stall
    Yu C, Gan H, Han J, Zhou ZX, Jia S, Chabes A, Farrugia G, Ordog T, Zhang Z
    Mol Cell. 2014.
    PMID: 25449133, DOI: 10.1016/j.molcel.2014.09.017
  10. A Cul4 E3 ubiquitin ligase regulates histone hand-off during nucleosome assembly
    Han J, Zhang H, Zhang H, Wang Z, Zhou H, Zhang Z
    Cell. 2013.
    PMID: 24209620, DOI: 10.1016/j.cell.2013.10.014
  11. The histone H3.3K27M mutation in pediatric glioma reprograms H3K27 methylation and gene expression
    Chan KM, Fang D, Gan H, Hashizume R, Yu C, Schroeder M, Gupta N, Mueller S, James CD, Jenkins R, Sarkaria J, Zhang Z
    Genes Dev. 2013.
    PMID: 23603901, DOI: 10.1101/gad.217778.113
  12. Structural basis for recognition of H3K56-acetylated histone H3-H4 by the chaperone Rtt106
    Su D, Hu Q, Li Q, Thompson JR, Cui G, Fazly A, Davies BA, Botuyan MV, Zhang Z, Mer G
    Nature. 2012.
    PMID: 22307274, DOI: 10.1038/nature10861
  13. Acetylation of histone H3 lysine 56 regulates replication-coupled nucleosome assembly
    Li Q, Zhou H, Wurtele H, Davies B, Horazdovsky B, Verreault A, Zhang Z
    Cell. 2008.
    PMID: 18662540, DOI: 10.1016/j.cell.2008.06.018
  14. Rtt109 acetylates histone H3 lysine 56 and functions in DNA replication
    Han J, Zhou H, Horazdovsky B, Zhang K, Xu RM, Zhang Z
    Science. 2007.
    PMID: 17272723, DOI: 10.1126/science.1133234

For a complete list of publications, please visit PubMed.gov