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
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