Research Overview:

The number of men affected by prostate cancer is staggering. In North America, there are approximately 200,000 cases of prostate cancer every year and around 32,000 deaths. This translates into a 1 in 6 lifetime chance of acquiring prostate cancer if you are an American male. Initially, prostate cancer is sensitive to the levels of male steroid hormones or androgens. Removal of the androgens, by surgical or chemical castration, is still a gold standard for prostate cancer therapy. For a time, the cancer responds by regressing under the conditions of androgen deprivation, however, the cancer eventually adapts and continues growing in the absence or reduced levels of androgens. The tumor has now shifted from being androgen dependent or sensitive to androgen independent. The development of metastases, tumor deposits away from the initial prostate cancer, along with the shift from androgen dependent to androgen independent is termed progression.

Research in my laboratory is concerned with the mechanism(s) that contribute to the development of prostate cancer or cancer ontogeny. As the cancer becomes more aggressive this includes the mechanisms and adaptations that lead to the development of bone metastases and androgen independence. In working towards an understanding of prostate cancer development and progression, my lab has two areas of emphasis 1) stromal-epithelial cell interaction and 2) oncofetal translational genomics. Stromal-epithelial interactions include interactions between prostate epithelial and stromal cells as well as between prostate epithelial cells and the bone microenvironment. These interactions are mediated by growth factors, like IGF-I and EGF, as well as steroid hormones, like androgens and estrogens. These factors can dramatically affect the ability of a cell to live or die in response to chemotherapy or other genotoxic stress. Oncofetal translational genomics is a phrase that can be distilled to mean that a cancer cell may inappropriately express genes or gene products that were responsible for regulating the growth or development of the fetal prostate. As these genes/gene products are misexpressed in prostate cancer, the prostate cancer cell may lose the ability to regulate its growth or state of differentiation. My lab is in the process of identifying fetal prostate genes that are candidates for temporal or spatial misexpression.

Finally, since there is no good therapy for advanced prostate cancer my lab has an active program in therapeutic drug discovery/validation. Current preclinical research is evaluating a novel class of sodium channel inhibitors. In collaboration with Dr. Milton Brown, UVA Dept. of Chemistry, we have found several lead compounds that dramatically decrease prostate cancer cell growth in both two-dimensional and three-dimensional growth assays. Selected compounds will soon enter preclinical animal modeling. Additional areas for future studies include na’aladase inhibitors and anti-angiogenic compounds.

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