Research Interests The genetics of prostate cancer in African-American men: We are interested in gene expression responsible for the clinical differences in prostate cancer presentation between Caucasian and African-American men. We are actively engaged in studies using comparative genomic hybridization (CGH), FISH, and micro-array (cDNA and tissue) analysis to screen patient samples for differences in gene expression that may be involved in tumor angiogenesis and metastasis. Regulation of Tumor Progression:1. Angiogenesis: Prostate and bladder tumors have increased expression of the translation initiation factor, eIF4E, which in turn increases the translation efficiency of pro-angiogenic factors like vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (FGF-2). A second novel positive regulator of angiogenesis is the tissue inhibitor of metalloproteinase-1 gene (TIMP-1), which is overexpressed in a large number of prostate tumors, predominately from African-American men. TIMP-1 dramatically increases VEGF transcription as well as affecting other potential angiogenic genes downstream of TIMP-1 overexpression, such as Ras.2. Metastasis: We are also trying to identify pro-invasion and pro-metastatic factors besides angiogenic factors that are regulated by eIF4E levels. We have found several tumor proteases that are regulated by eIF4E levels and are testing them for clinical relevance. TIMP-1 also increases tumor cell invasion by altered trafficking of proteolytic enzymes. Gene and other Experimental Therapies: 1. Anti-eIF4E: using siRNA or antisense approaches. 2. PSMA-directed: Immunomodulatory gene therapy for vaccine development. 3. Translationally regulated: toxic therapies for bladder and prostate cancer. 4. Novel viruses: cytolytic Sindbis virus for bladder and prostate cancer. 5. NFkB inhibitors/copper chelator: tetrathiomolybdate to inhibit bone metastases.
Specialized Techniques/Procedures FISH, CGH (comparative genomic hybridization) PCR, RT-PCR Micro-array analysis; cDNA and tissue Motility & Invasion assays Immunohistochemistry, Immunofluorescence & high-resolution microscopy Animal studies of tumor growth, angiogenesis, and metastasis