Michael M. Shen, PhD

Profile Headshot

Overview

The Shen laboratory investigates the molecular mechanisms of mammalian development and cancer using in vivo analyses of genetically-engineered mouse models. The lab’s studies have expanded significantly to encompass analyses of prostate epithelial progenitor cells and their roles in organogenesis and tissue regeneration, focusing on the role of the Nkx3.1 transcriptional regulator as well as analysis of cell types of origin for prostate cancer. These studies have led to the identification of a luminal epithelial stem cell as well as support for a luminal cell of origin for prostate cancer, and most recently to the establishment of an organoid culture system for mouse and human prostate epithelium.

Dr. Shen’s research has also incorporated bioinformatic and computational systems approaches in studies ranging from analyses of extraembryonic endoderm stem cell differentiation to the investigation of prostate epithelial lineage specification. Ongoing projects include systems analyses of embryonic stem cell pluripotency, investigation of mechanisms of prostate epithelial lineage specification and cell-type differentiation, and generation of novel mouse models of advanced prostate cancer. Most recently, the scope of Dr. Shen’s research has expanded to molecular studies of bladder cancer evolution and drug response through the analysis of patient-derived bladder tumor organoids.

Academic Appointments

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

Administrative Titles

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

Credentials & Experience

Education & Training

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

Research

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

TOPOLOGY OF CANCER EVOLUTION AND HETEROGENEITY (Federal Gov)

May 19 2015 - Apr 30 2021

SYSTEMS ANALYSIS OF MOUSE GASTRULATION (Federal Gov)

Jul 10 2016 - Apr 30 2021

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

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

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

Apr 1 2015 - Mar 31 2017

TARGETING GENOMIC INSTABILITY IN SPOP MUTANT PROSTATE CANCER (Private)

Jan 1 2015 - Dec 31 2016

MOLECULAR MECHANISMS OF PROSTATE CANCER INITIATION (Federal Gov)

Sep 16 2011 - Aug 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

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

Jan 1 2015 - Dec 31 2015

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

Sep 1 2010 - Aug 31 2013

IDENTIFICATION OF MASTER REGULATORS FOR STEM CELL PLURIPOTEN CY AND SELF-RENEWAL (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

Selected Publications

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.

Chu, J., and Shen, M. M. (2010). Functional redundancy of EGF-CFC genes in epiblast and extraembryonic patterning during early mouse embryogenesis. Dev. Biol. 342: 63-73. PMCID: PMC2866749.

Shen, M. M., and Abate-Shen, C. (2010). Molecular genetics of prostate cancer: new prospects for old challenges. Genes Dev. 24: 1967-2000. PMCID: PMC2939361.

Kruithof-de Julio, M., Alvarez, M. J., Galli, A., Chu, J., Price, S. M., Califano, A., and Shen, M. M. (2011). Regulation of extraembryonic endoderm stem cell differentiation by Nodal and Cripto signaling. Development 138: 3885-3895. PMCID: PMC3160087.

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.

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., 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.

Toivanen, R., Mohan, A., and Shen, M. M. (2016). Basal progenitors contribute to repair of the prostate epithelium following induced luminal anoikis. Stem Cell Rep. 6: 660-667. PMCID: PMC4939748.

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. PMCID: PMC5501744.

Toivanen, R., and Shen, M. M. (2017). Prostate organogenesis: tissue induction, hormonal regulation and cell type specification. Development 144: 1382-1398. PMCID: PMC5399670.

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.

Chua, C. W., Epsi, N. J., Leung, E. Y., Xuan, S., Lei, M., Li, B. I., Bergren, S. K., Hibshoosh, H., Mitrofanova, A., and Shen, M. M.(2018). Differential requirements of androgen receptor in luminal progenitors during prostate regeneration and tumor initiation. eLife 7: e28768. PMCID: PMC5807048.

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.