Michael M. Shen, PhD

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Overview


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.     

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

Selected 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.