Michael M. Shen, PhD

Academic Appointments

  • Professor of Medical Sciences (in Medicine)
  • Professor of Genetics & Development

Current Administrative Positions

  • Director of Graduate Studies, Department of Genetics & Development
  • Co-Leader, Tumor Biology and Microenvironment, Herbert Irving Comprehensive Cancer Center
Michael M. Shen, PhD


During the past twenty-seven years, my laboratory has investigated fundamental mechanisms of mammalian development and cancer using in vivo analyses of genetically-engineered mouse and organoid models. After starting my lab at Rutgers-Robert Wood Johnson Medical School in 1994, my group pursued functional analyses of the EGF-CFC co-receptors for the TGF-beta ligand Nodal, and elucidated their essential roles in establishing the mammalian body plan. 

After moving to Columbia University Irving Medical Center (CUIMC) in 2007, our research program expanded significantly to encompass analyses of the hormonal regulation of prostate development and cancer, including studies of the Nkx3.1 transcriptional regulator as well as pathways of epithelial lineage specification during organogenesis and tissue regeneration. This work identified luminal epithelial progenitors in the prostate and showed that luminal cells are favored as the cell of origin for prostate cancer. More recently, we generated novel culture conditions for mouse and human prostate and bladder organoids, which led to creation of a biobank of patient-derived bladder tumor organoids that has provided a platform for translational studies of tumor evolution and drug resistance. Recent projects in the laboratory have incorporated single-cell and computational systems approaches in analyses of mechanisms of epithelial differentiation and transdifferentiation in prostate cancer, and in studies of tumor plasticity in bladder cancer. Our current efforts focus on understanding molecular mechanisms of cell type specification in the normal as well as transformed prostate epithelium, the epigenetic regulation of lineage plasticity in both bladder and prostate cancer, and the role of the tumor microenvironment in modulating treatment response.     

Departments and Divisions

  • Department of Medicine
    Division of Hematology/Oncology
  • Department of Genetics & Development

Education and Training

  • BA, 1984 Biochemical Sciences, Harvard University
  • PhD, 1988 Genetics, Cambridge University
  • Fellowship: 1994 Harvard Medical School

Centers / Institutes / Programs

  • Herbert Irving Comprehensive Cancer Center
  • Columbia Stem Cell Initiative

Lab Locations

  • Irving Cancer Research Center

    1130 St. Nicholas Avenue
    New York, NY 10032

NIH Grants

  • INVESTIGATING LINEAGE PLASTICITY IN CASTRATION-RESISTANT PROSTATE CANCER (Federal Gov)

    Jul 1 2020 - Jun 30 2025

    ANALYSIS OF EPITHELIAL HETEROGENEITY IN PROSTATE DEVELOPMENT AND CANCER (Federal Gov)

    Apr 1 2019 - Mar 31 2024

    MODELING BLADDER CANCER PATHOGENESIS AND TUMOR EVOLUTION (Federal Gov)

    Sep 11 2018 - Aug 31 2023

    A CO-CLINICAL TRIAL OF CHEMOTHERAPY RESPONSE IN BLADDER CANCER USING PATIENT-DERIVED TUMOR ORGANOIDS (Private)

    Nov 1 2018 - Oct 31 2021

    CENTERS FOR CANCER SYSTEMS THERAPEUTICS (CAST) (Federal Gov)

    Aug 8 2016 - Jul 31 2021

    PREDOCTORAL TRAINING GRANT IN GENETICS AND DEVELOPMENT (Federal Gov)

    Jul 1 2016 - Jun 30 2021

    SYSTEMS ANALYSIS OF MOUSE GASTRULATION (Federal Gov)

    Jul 10 2016 - Apr 30 2021

    TOPOLOGY OF CANCER EVOLUTION AND HETEROGENEITY (Federal Gov)

    May 19 2015 - Apr 30 2021

    THET.J. MARTELL FOUNDATION FOR LEUKEMIA, CANCER AND AIDS RESEARCH (Private)

    Jan 1 2015 - Dec 31 2020

    MASTER REGULATORS UNDERLYING TUMOR MICROENVIRONMENT INTERACTIONS IN LOCALIZED AND METASTATIC PROSTATECANCER (Private)

    Nov 2 2018 - Nov 2 2020

    INVESTIGATING THE CELL OF ORIGIN OF BLADDER CANCER (Federal Gov)

    Apr 1 2015 - Sep 30 2020

    MODELING BLADDER CANCER METASTASIS USING HUMAN PATIENT-DERIVED TUMOR ORGANOIDS (Private)

    Aug 15 2018 - Aug 15 2020

    IDENTIFICATION OF MASTER TRANSCRIPTIONAL REGULATORS OF NEUROENDOCRINE DIFFERENTIATION IN PROSTATE CANCER (Federal Gov)

    Jul 30 2018 - Jun 29 2020

    TOPOLOGY OF CANCER EVOLUTION AND HETEROGENEITY (Federal Gov)

    May 19 2015 - Apr 30 2020

    TOPOLOGY OF CANCER EVOLUTION AND HETEROGENEITY (Federal Gov)

    May 19 2015 - Apr 30 2020

    INVESTIGATING THE CELL OF ORIGIN OF BLADDER CANCER (Federal Gov)

    Apr 1 2015 - Mar 31 2020

    INVESTIGATION OF A PUTATIVE PROSTATE STEM CELL NICHE (Federal Gov)

    Sep 1 2016 - Aug 31 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

    ANALYSIS OF DRUG RESPONSE IN ORGANOIDS AND MOUSE MODELS (Federal Gov)

    Jul 1 2016 - Jun 30 2019

    CANCER CENTER SUPPORT GRANT (Federal Gov)

    Jul 1 2014 - Jun 30 2019

    TOWARDS UNDERSTANDING PROSTATE CANCER HETEROGENEITY (Federal Gov)

    Aug 1 2017 - Jul 31 2018

    CULTURE OF PATIENT-DERIVED BLADDER CANCER ORGANOIDS (Private)

    Jul 1 2016 - Jun 30 2018

    IDENTIFICATION OF MASTER REGULATORS OF ADVANCED AND CASTRATE-RESISTANT PROSTRATE CANCER UNDER TREATMENT WITH ABIRATERONE. (Federal Gov)

    Sep 30 2013 - Sep 29 2017

    IDENTIFICATION AND VALIDATION OF MASER REGULATORS OF CASTRATION RESISTANT PROSTATE CANCER (Federal Gov)

    Sep 1 2015 - Aug 31 2017

    EPIGENETIC REGULATION OF BLADDER CANCER PROGRESSION (Private)

    Jul 15 2015 - Jul 14 2017

    MODELING HUMAN PROSTATE CANCER BY CELLULAR REPROGRAMMING (Federal Gov)

    Jul 1 2015 - Jun 30 2017

    MODELING HUMAN PROSTATE CANCER BY CELLULAR REPROGRAMMING (Federal Gov)

    Jul 1 2015 - Jun 30 2017

    INVESTIGATION OF LUMINAL STEM CELLS AND CASTRATION RESISTANCE IN PROSTATE CANCER (Federal Gov)

    Apr 1 2015 - Mar 31 2017

    PROGENITOR CELLS OF THE MOUSE PROSTATE EPITHELIUM (Federal Gov)

    Jul 1 2006 - Mar 31 2017

    PROGENITOR CELLS OF THE MOUSE PROSTATE EPITHELIUM (Federal Gov)

    Jul 1 2006 - Mar 31 2017

    PROGENITOR CELLS OF THE MOUSE PROSTATE EPITHELIUM (Federal Gov)

    Jul 1 2006 - Mar 31 2017

    MOLECULAR MECHANISMS OF PROSTATE CANCER INITIATION (Federal Gov)

    Sep 16 2011 - Feb 28 2017

    TARGETING GENOMIC INSTABILITY IN SPOP MUTANT PROSTATE CANCER (Private)

    Jan 1 2015 - Dec 31 2016

    INVESTIGATION OF HUMAN PROSTATE CANCER PROGRESSION AND TREATMENT RESPONSE USING A NOVEL GENETICALLY ENGINEERED CULTURE MODEL (Federal Gov)

    Aug 19 2014 - Aug 18 2016

    INVESTIGATION OF CYSVIEW CYTOTOXICITY FOR HUMAN BLADDER ORGANOIDS (Private)

    Aug 1 2015 - Jul 31 2016

    NATIONAL CENTER: MULTISCALE ANALYSIS OF GENOMIC AND CELLULAR NETWORKS (MAGNET) (Federal Gov)

    Sep 26 2005 - Jul 31 2016

    INVESTIGATING THE CELL OF ORIGIN OF BLADDER CANCER (Federal Gov)

    Apr 1 2015 - Mar 31 2016

    INVESTIGATING THE CELL OF ORIGIN OF BLADDER CANCER (Federal Gov)

    Apr 1 2015 - Mar 31 2016

    HIPPO SIGNALING IN PROSTATE REGENERATION AND CANCER (Federal Gov)

    Sep 1 2012 - Aug 31 2014

    ELUCIDATION OF CANCER PATHWAYS AND DRUGGABLE TARGETS USING MOUSE MODELS (Federal Gov)

    Sep 30 1999 - Jul 31 2014

    DIRECTED DIFFERENTIATION AND TRANSDIFFERENTATION TO PROSTATE AND BLADDER EPITHELIA (Private)

    Jul 1 2012 - Jun 30 2014

    A NOVEL MODEL SYSTEM FOR ASSAYING DRUG RESPONSES OF HUMAN PROSTATE CANCER (Private)

    Jul 1 2013 - Jun 30 2014

    FUNCTIONAL ANALYSIS OF E-CADHERIN IN PROSTATE CANCER PROGRESSION (Federal Gov)

    Mar 1 2012 - Feb 28 2014

    IDENTIFICATION OF MASTER REGULATORS FOR STEM CELL PLURIPOTEN CY AND SELF-RENEWAL (NY State Gov)

    Sep 1 2010 - Aug 31 2013

    IDENTIFICATION AND ANALYSIS OF PROSTATE TUMOR INITIATING CEL LS (NY State Gov)

    Sep 1 2010 - Aug 31 2013

    FUNCTIONAL ANALYSIS OF ANDROGEN RECEPTOR IN PROSTATE EPITHELIAL STEM CELLS (Federal Gov)

    Jun 1 2011 - Jun 30 2013

    LINEAGE ANALYSIS OF CELLS OF ORIGIN FOR PROSTATE CANCER (Federal Gov)

    Jun 1 2011 - May 31 2013

    FUNCTIONAL ANALYSIS OF CRIPTO IN MOUSE EMBRYOGENESIS (Federal Gov)

    Apr 1 1998 - Apr 30 2013

    NEXT-GENERATION MOUSE MODELS FOR STUDYING PROSTATE CANCER IN ITIATION AND PROGRESSION (Federal Gov)

    Jun 1 2009 - Jun 30 2012

    IDENTIFICATION OF MASTER REGULATORS FOR STEM CELL PLURIPOTEN CY AND SELF-RENEWAL (NY State Gov)

    Apr 1 2010 - Mar 31 2012

Lab Members

Terri Rosa

Shouhong Xuan

Bomiao Hu

Jia Li

Laura Crowley

Weiping Li

John Christin

Jinqiu Lu

Talal Syed

Publications

Crowley, L., Cambuli, F., Aparicio, L., Shibata, M., Robinson, B. D., Xuan, S., Li, W., Hibshoosh, H., Loda, M., Rabadan, R., and Shen, M. M. (2020). A single-cell atlas of the mouse and human prostate reveals heterogeneity and conservation of epithelial progenitors. eLife 9: e59465. PMCID: PMC7529463.

Lee, S. H., Hu, W., Matulay, J. T., Silva, M. V., Owczarek, T. B., Kim, K., Chua, C. W., Barlow, L. J., Kandoth, C., Williams, A. B., Bergren, S. K., Pietzak, E. J., Anderson, C. B., Benson, M. C., Coleman, J. A., Taylor, B. S., Abate-Shen, C., McKiernan, J. M., Al-Ahmadie, H., Solit, D. B., and Shen, M. M. (2018). Tumor evolution and drug response in patient-derived organoid models of bladder cancer. Cell 173: 515-528. PMCID: PMC5890941.

Zou, M., Toivanen, R., Mitrofanova, A., Floc’h, N., Hayati, S., Sun, Y., Le Magnen, C., Chester, D., Mostaghel, E. A., Califano, A., Rubin, M. A., Shen, M. M.*, and Abate-Shen, C. (2017). Transdifferentiation as a mechanism of treatment resistance in a mouse model of castration-resistant prostate cancer. Cancer Discov. 7: 736-749. (*co-corresponding author)

Talos, F., Mitrofanova, A., Bergren, S. K., Califano, A., and Shen, M. M. (2017). A computational systems approach identifies synergistic specification genes that facilitate lineage conversion to prostate tissue. Nat. Comm. 8: 14662. PMCID: PMC5413950.

Wang, Z. A., Toivanen, R., Bergren, S. K., Chambon, P., and Shen, M. M. (2014). Luminal cells are favored as the cell of origin for prostate cancer. Cell Rep. 8: 1339-1346. PMCID: PMC4163115.

Chua, C. W., Shibata, M., Lei, M., Toivanen, R., Barlow, L. J., Bergren, S. K., Badani, K. K., McKiernan, J. M., Benson, M. C., Hibshoosh, H., and Shen, M. M. (2014). Single luminal epithelial progenitors can generate prostate organoids in culture. Nat. Cell Biol. 16: 951-961. PMCID: PMC4183706.

Wang, Z. A., Mitrofanova, A., Bergren, S. K., Abate-Shen, C., Cardiff, R. D., Califano, A., and Shen, M. M. (2013). Lineage analysis of basal epithelial cells reveals their unexpected plasticity and supports a cell of origin model for prostate cancer heterogeneity. Nat. Cell Biol. 15: 274-283. PMCID: PMC3743266.

Wang, X., Kruithof-de Julio, M., Economides, K. D., Walker, D., Yu, H., Halili, M. V., Hu, Y.-P., Price, S. M., Abate-Shen, C., and Shen, M. M. (2009). A luminal epithelial stem cell that is a cell of origin for prostate cancer. Nature 461: 495-500. PMCID: PMC2800362.

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