The Prostate Cancer Stem Cell Lab
By employing prostate cancer (PCa) as a model system, our lab studies general principles governing cancer stem cell (CSC) development that generates the cellular heterogeneity of the tumor. Our work suggests that PCa cells are not all equal with respect to their tumorigenic and metastatic potential. Rather, PCa cells with many hardcore stem-cell properties exist. These stem-like PCa cells (i.e., PCSCs) are mostly undifferentiated lacking the expression of PSA, preferentially express stem cell-associated genes and epigenetic landmarks, can undergo asymmetric cell division and regenerate differentiated cells, are more quiescent and resistant to castration and other clinical and experimental therapeutics, and can re-create the PCa cell heterogeneity in the tumors. The lab currently focuses on: role of normal prostate stem/progenitor cells in PCa development; mechanisms of PCSC self-renewal and cell division (i.e., symmetric vs. asymmetric); the epigenetic landscape in and epigenetic regulation (e.g., by miRNAs) of PCSCs; role of PCSCs in therapeutic resistance, castration-resistant disease, and distant metastasis; and developing novel therapeutics targeting PCSCs. These projects employ xenograft tumors, primary tumor samples, as well as genetic mouse models. The ultimate goal of our research is to uncover the unique properties of PCSCs and design specific therapeutics such as monoclonal antibodies and chemical drugs to target PCSCs.