Wei Gu, PhD

Academic Appointments

  • Abraham and Mildred Goldstein Professor of Pathology and Cell Biology (in the Institute for Cancer Genetics)
Wei Gu, PhD

Email: wg8@cumc.columbia.edu

Over the past 20 years, the integrative approach of the Gu Laboratory, combining biochemical analyses and advanced genetically manipulated mouse models has been instrumental to dissect the precise roles of protein modifications in regulating p53-mediated tumor suppression. The Gu lab has made significant contributions to establishing the roles of acetylation-mediated regulation of non-histone proteins. They established that site-specific acetylation plays a critical role in promoter-specific regulation of p53 targets. They discovered that the acidic domain containing proteins act as a new “reader” for acetylated substrates critically involved in acetylation-mediated actions. These studies have laid the foundation for the view that reversible acetylation is a general mechanism for regulation of non-histone proteins. Through in-depth investigation, the Gu lab has revealed that “dynamic ubiquitination” (polyubiquitination, monoubiquitination and deubiquitination) is the major mechanism by which the stability and subcellular localization of p53 protein are determined. They found that the deubiquitinase USP7 (also called HAUSP) interacts with both p53 and Mdm2; and is an important therapeutic target for human cancers through activating p53 and downregulating oncoproteins such as N-Myc. By using p53 acetylation-deficient mutant mice, the Gu lab has demonstrated that acetylation is required for p53-mediated cell-cycle arrest, senescence and apoptosis in vivo. Subsequently, they found that p53 is able to induce its tumor suppression through its metabolic targets including promoting ferroptosis.

Departments and Divisions

  • Department of Pathology & Cell Biology

Centers / Institutes / Programs

  • Herbert Irving Comprehensive Cancer Center

Past Positions

1995 -1998 LSRF (Life Science Research Foundation) Advanced Cancer Research Fellow

Dr. Robert G. Roeder’s Lab, The Rockefeller University, New York, NY

1999 -2004 Assistant Professor (Tenure-track), Columbia University Medical Center, New York, NY

1999 -Present Principal Investigator/Member, Columbia University Herbert Irvine Cancer Center

2004 -2006 Associate Professor (Tenured)

2007-present Professor, Institute for Cancer Genetics, and Dept. of Pathology and Cell Biology Columbia University Medical Center

Ad Hoc. NIH Tumor Progression and Metastasis Study section (TPM)

Ad Hoc. NIH Molecular Oncogenesis Study Section (MONC)

Ad Hoc. NIH Cancer Molecular Pathobiology Study Section (CAMP) and CSRS

Ad Hoc. NIH Cancer Etiology Study Section (CE)

Ad Hoc. NIH Cancer Molecular Pathobiology Study Section (CAMP) for

Challenge Grants

Ad Hoc. NIH Cancer Etiology Study Section (CE)

Ad Hoc. NIH Cancer Molecular Pathobiology Study Section (CAMP)

Keynote speaker of the 2011-Mdm2/Mdmx international conference.

Special Emphasis Panel for R15 (AREA) application OBT study section.

2013-2017 Charter Member of NIH Cancer Mole Pathology study Section (CAMP).

2013-present Abraham and Mildred Goldstein Endowed Chair

Professor of Pathology and Cell Biology, Columbia University, New York

2013-present Vice-Chairman for Cancer Research in the

Department of Pathology and Cell Biology, Columbia University

2013-1015 Molecular and Cellular Biology Subcommittee Member of the AACR Program Committee

2014-2015 AACR Basic Cancer Research Fellowships Scientific Review Committee

NIH Grants

  • REGULATION OF P53 ACETYLATION AND DEACETYLATION IN TUMORIGENESIS. (Federal Gov)

    Dec 1 2019 - Nov 30 2024

    P53 ACETYLATION IN FERROPTOSIS AND TUMOR SUPPRESSION (Federal Gov)

    Dec 1 2017 - Nov 30 2022

    MECHANISMS OF TARGETING ONCOPROTEIN SET IN TUMOR SUPPRESSION (Federal Gov)

    Apr 1 2017 - Mar 31 2022

    HAUSP INHIBITORS IN P53-WILD TYPE AND P53-MUTANT TUMORS (Federal Gov)

    May 1 2015 - Apr 30 2021

    REGULATION OF SLC7A11 BY P53 IN CANCER METABOLISM (Federal Gov)

    Dec 1 2015 - Nov 30 2020

    REGULATION OF P53 ACETYLATION AND DEACETYLATION IN TUMORIGENESIS (Federal Gov)

    Aug 1 2014 - Jul 31 2020

    HAUSP INHIBITORS IN P53-WILD TYPE AND P53-MUTANT TUMORS (Federal Gov)

    May 1 2015 - Apr 30 2020

    REGULATION OF P53 ACETYLATION AND DEACETYLATION IN TUMORIGENESIS (Federal Gov)

    Aug 1 2014 - Jul 31 2019

    REGULATION OF P53 ACETYLATION AND DEACETYLATION IN TUMORIGENESIS (Federal Gov)

    Aug 1 2014 - Jul 31 2019

    ROLE OF P53-MEDIATED UNCONVENTIONAL FUNCTIONS IN TUMOR SUPPRESSION (Federal Gov)

    Sep 26 2012 - Aug 31 2017

    MECHANISMS OF NOVEL CANCER TARGETS IN ARF-MEDIATED TUMOR SUPPRESSION (Federal Gov)

    Sep 1 2012 - Aug 31 2017

    MECHANISMS OF NOVEL CANCER TARGETS IN ARF-MEDIATED TUMOR SUPPRESSION (Federal Gov)

    Sep 1 2012 - Aug 31 2017

    MECHANISMS OF NOVEL CANCER TARGETS IN ARF-MEDIATED TUMOR SUPPRESSION (Federal Gov)

    Sep 1 2012 - Aug 31 2017

    ROLE OF P53-MEDIATED UNCONVENTIONAL FUNCTIONS IN TUMOR SUPPRESSION (Federal Gov)

    Sep 26 2012 - Aug 31 2017

    ROLE OF P53-MEDIATED UNCONVENTIONAL FUNCTIONS IN TUMOR SUPPRESSION (Federal Gov)

    Sep 26 2012 - Aug 31 2017

    REGULATION OF MDMX STABILITY AND SUBCELLULAR LOCALIZATION BY UBIQUITINATION (Federal Gov)

    Aug 14 2012 - Jul 31 2017

    REGULATION OF MDMX STABILITY AND SUBCELLULAR LOCALIZATION BY UBIQUITINATION (Federal Gov)

    Aug 14 2012 - Jul 31 2017

    REGULATION OF MDMX STABILITY AND SUBCELLULAR LOCALIZATION BY UBIQUITINATION (Federal Gov)

    Aug 14 2012 - Jul 31 2017

    REGULATION OF MDMX STABILITY AND SUBCELLULAR LOCALIZATION BY UBIQUITINATION (Federal Gov)

    Aug 14 2012 - Jul 31 2017

    MOLECULAR PATHOGENESIS OF BASAL-LIKE BREAST CANCER (Federal Gov)

    Jul 1 2002 - Aug 31 2015

    MECHANISMS OF MDM2/MDMX IN REPRESSING P53 (Federal Gov)

    Jan 1 2009 - Dec 31 2014

    P53-MEDIATED TUMOR SUPPRESSION THROUGH TNFRSF14 REGULATION LYMPHOMA (Private)

    Sep 1 2014 - Sep 30 2014

    P53 REGULATORS AND EFFECTORS PROJECT 2 ANTI-REPRESSION MECHANISMS IN P53-MEDIATED STRESS RESPONSES (Federal Gov)

    Sep 14 2010 - Jun 30 2014

    SUBPROJECT FOR INSTITUTION # 08-8993 (Private)

    Oct 1 2008 - Sep 30 2013

    DYNAMIC ROLES OF HAUSP IN P53/MDM2 REGULATION (Federal Gov)

    Jul 1 2007 - May 31 2013

    MECHANISMS OF P53 ACTIVATION IN TUMOR SUPPRESSION (Federal Gov)

    May 15 2003 - Apr 30 2013

    MECHANISMS OF P53 ACTIVATION IN TUMOR SUPPRESSION (Federal Gov)

    May 15 2003 - Apr 30 2013

    DIABETES AND ENDOCRINOLOGY RESEARCH CENTER (Federal Gov)

    May 1 2003 - Jan 31 2013

    THE ROLE OF ARF-BP1 IN TUMORIGENESIS (Federal Gov)

    Mar 24 2006 - Mar 31 2012

    REGULATION OF SIRT1 IN STRESS RESPONSES AND AGING (Private)

    Nov 1 2007 - Oct 31 2011

Publications

  1. ALOX12 is required for p53-mediated tumour suppression through a distinct ferroptosis pathway
    Chu B, Kon N, Chen D, Li T, Liu T, Jiang L, Song S, Tavana O, Gu W
    Nat Cell Biol. 2019.
    PMID: 30962574, DOI: 10.1038/s41556-019-0305-6
  2. NRF2 Is a Major Target of ARF in p53-Independent Tumor Suppression
    Chen D, Tavana O, Chu B, Erber L, Chen Y, Baer R, Gu W
    Mol Cell. 2017.
    PMID: 28985506, DOI: 10.1016/j.molcel.2017.09.009
  3. Acetylation-regulated interaction between p53 and SET reveals a widespread regulatory mode
    Wang D, Kon N, Lasso G, Jiang L, Leng W, Zhu WG, Qin J, Honig B, Gu W
    Nature. 2016.
    PMID: 27626385, DOI: 10.1038/nature19759
  4. HAUSP deubiquitinates and stabilizes N-Myc in neuroblastoma
    Tavana O, Li D, Dai C, Lopez G, Banerjee D, Kon N, Chen C, Califano A, Yamashiro DJ, Sun H, Gu W
    Nat Med. 2016.
    PMID: 27618649, DOI: 10.1038/nm.4180
  5. Ferroptosis as a p53-mediated activity during tumour suppression
    Jiang L, Kon N, Li T, Wang SJ, Su T, Hibshoosh H, Baer R, Gu W
    Nature. 2015.
    PMID: 25799988, DOI: 10.1038/nature14344
  6. Tumor suppression in the absence of p53-mediated cell-cycle arrest, apoptosis, and senescence
    Li T, Kon N, Jiang L, Tan M, Ludwig T, Zhao Y, Baer R, Gu W
    Cell. 2012.
    PMID: 22682249, DOI: 10.1016/j.cell.2012.04.026
  7. Acetylation is indispensable for p53 antiviral activity
    Muñoz-Fontela C, González D, Marcos-Villar L, Campagna M, Gallego P, González-Santamaría J, Herranz D, Gu W, Serrano M, Aaronson SA, Rivas C
    Cell Cycle. 2011.
    PMID: 22033337, DOI: 10.4161/cc.10.21.17899
  8. Transcription-independent ARF regulation in oncogenic stress-mediated p53 responses
    Chen D, Shan J, Zhu WG, Qin J, Gu W
    Nature. 2010.
    PMID: 20208519, DOI: 10.1038/nature08820
  9. Modes of p53 regulation
    Kruse JP, Gu W
    Cell. 2009.
    PMID: 19450511, DOI: 10.1016/j.cell.2009.04.050
  10. Negative regulation of the deacetylase SIRT1 by DBC1
    Zhao W, Kruse JP, Tang Y, Jung SY, Qin J, Gu W
    Nature. 2008.
    PMID: 18235502, DOI: 10.1038/nature06515
  11. ARF-BP1/Mule is a critical mediator of the ARF tumor suppressor
    Chen D, Kon N, Li M, Zhang W, Qin J, Gu W
    Cell. 2005.
    PMID: 15989956, DOI: 10.1016/j.cell.2005.03.037
  12. Mono- versus polyubiquitination: differential control of p53 fate by Mdm2
    Li M, Brooks CL, Wu-Baer F, Chen D, Baer R, Gu W
    Science. 2003.
    PMID: 14671306, DOI: 10.1126/science.1091362
  13. Deubiquitination of p53 by HAUSP is an important pathway for p53 stabilization
    Li M, Chen D, Shiloh A, Luo J, Nikolaev AY, Qin J, Gu W
    Nature. 2002.
    PMID: 11923872, DOI: 10.1038/nature737
  14. Negative control of p53 by Sir2alpha promotes cell survival under stress
    Luo J, Nikolaev AY, Imai S, Chen D, Su F, Shiloh A, Guarente L, Gu W
    Cell. 2001.
    PMID: 11672522, DOI: 10.1016/s0092-8674(01)00524-4
  15. Deacetylation of p53 modulates its effect on cell growth and apoptosis
    Luo J, Su F, Chen D, Shiloh A, Gu W
    Nature. 2000.
    PMID: 11099047, DOI: 10.1038/35042612

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