Shen Lab

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.