Michael M. Shen, PhD
- Professor of Medical Sciences (in Medicine)
- Professor of Genetics & Development
- Director of Graduate Studies, Department of Genetics & Development
- Co-Leader, Tumor Biology and Microenvironment, Herbert Irving Comprehensive Cancer Center
The Shen laboratory investigates the molecular mechanisms of mammalian development and cancer using in vivo analyses of genetically-engineered mouse models. The labâ€™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. Shenâ€™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. Shenâ€™s research has expanded to molecular studies of bladder cancer evolution and drug response through the analysis of patient-derived bladder tumor organoids.
Credentials & Experience
Education & Training
- BA, 1984 Biochemical Sciences, Harvard University
- PhD, 1988 Genetics, Cambridge University
- Fellowship: Harvard Medical School
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
A REVERSE ENGINEERING APPROACH TO INVESTIGATE DRIVERS OF THERAPY RESISTANCE IN A CO-CLINICAL STUDY OF BLADDER CANCER USING PATIENT-DERIVED ORGANOIDS. (Private)
Jul 1 2020 - Jun 30 2021
TOPOLOGY OF CANCER EVOLUTION AND HETEROGENEITY (Federal Gov)
May 19 2015 - Apr 30 2021
MODELING BLADDER CANCER METASTASIS USING HUMAN PATIENT-DERIVED TUMOR ORGANOIDS (Private)
Aug 15 2018 - Feb 15 2021
THE T.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 - Jun 30 2020
CANCER CENTER SUPPORT GRANT (Federal Gov)
Jul 1 2014 - Jun 30 2020
IDENTIFICATION OF MASTER TRANSCRIPTIONAL REGULATORS OF NEUROENDOCRINE DIFFERENTIATION IN PROSTATE CANCER (Federal Gov)
Jul 30 2018 - Jun 29 2020
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.