Current Research and Scholarly Interests
The overall goal of my research is to develop realistic experimental models of benign and malignant prostatic diseases. Both benign prostatic hyperplasia (BPH) and prostate cancer (PCa) are major medical problems, causing significant morbidity and mortality. My lab has developed techniques to establish primary cultures of epithelial and stromal cells from normal, benign or malignant human prostatic tissues, and we have used these cell cultures to investigate many aspects of the molecular and cellular biology of the prostate. More recently, we have established tissue slice cultures (TSCs), which are live, precision-cut thin sections of tissues that can be maintained in culture for several days. TSCs are perhaps the most representative experimental model of the human prostate available, containing almost all of the cells typically present in the body and maintaining essential epithelial-stromal interactions as well as differentiated cells, which are typically lost in mono-culture. TSCs can also be established as grafts under the renal capsule of mice, providing an in vivo model of the benign and malignant prostate. In addition to our cell and tissue models, our research takes advantage of the archival patient materials available in the Department of Urology. These include tissues from a well-characterized series of radical prostatectomy specimens and a serum bank. Using these diverse models and resources, we carry out studies related to diagnosis, prognosis and treatment of PCa. Currently, some of our projects include: 1) investigating the association of a splice-variant of the androgen receptor with aggressive PCa, 2) studying cell surface proteoglycans as novel and specific biomarkers of PCa, 3) searching for serum autoantibodies or proteins that could be used to diagnose PCa, 4) creating induced pluripotent stem (iPS) cells from PCa cells as a novel model to characterize cancer-related methylation, 5) determining the role of monoamine oxidase A (MAOA) in normal prostate differentiation and as a therapeutic target, 6) using TSCs to screen phage display libraries to discover PCa-specific cell surface molecules for cancer-specific targeting, 7) developing hyperpolarized 13C-pyruvate magnetic resonance spectroscopic imaging for rapid evaluation of therapeutic response, 8) creating additional cell culture models of metastatic PCa, and 9) testing the efficacy of a novel organic arsenical compound against PCa. These projects are funded in part by the NIH, the DoD, and the Prostate Cancer Foundation.
