Personal Website

Project Description:

The long-term goal of our research program is to identify novel biomarkers of prostate cancer and to test their clinical utility either as diagnostic/prognostic factors, or as targets for therapeutic intervention. The approaches outlined in the present proposal focus on the identification of biomarkers for both early as well as progressive disease. We have chosen an integrative approach employing human prostatic tissues of pre- and early malignant nature, as well as more defined cell models of prostate cancer progression. We will focus primarily on markers that can be detected by immunohistochemical (IHC) analysis, i.e. proteins and lipids, an established diagnostic methodology in the clinics and on tissue microarrays (TMAs). We propose three Specific Aims that represent the progression of our project over three years:

First we will identify biomarkers in (i) epithelial and stromal cells derived from field cancerized tumor adjacent human prostatic tissues by generating proteomic expression profiles in comparison to disease-free prostatic tissues; and (ii) in the LNCaP>C4-2>C4-2B isogenic cell model of prostate cancer progression.

Second, using our collection of ~100 cases human prostatic tissues, we will generate prostatic TMAs of tumors, field cancerized matched adjacent tissues, and disease-free prostatic tissues, and validate potential biomarkers by immunohistochemistry. TMA analysis will allow us to determine the frequency, as well as cellular distribution of biomarker expression. The association of these parameters with clinicopathological patient information will evaluate the marker’s clinical diagnostic/prognostic utility.

Third, we will subject newly identified potential therapeutic targets to flow cytometric high throughput screening and cheminformatic validation of small molecule inhibitor libraries for the identification of lead compounds. Such compounds may represent novel treatment options in the preventive and/or adjunctive settting, for example in combination with androgen ablation and/or chemotherapy.

This integrated approach is driven by an experienced team of biomedical researchers and an established network of trans-disciplinary collaborators.