): This proposal is designed to provide the applicant, Peter Nelson, with the scientific tools and career development necessary for a successful career in academic medicine and basic science. Dr. Nelson has completed a combined hematology and oncology fellowship and is currently conducting research in Dr. Leroy Hood's laboratory at the University of Washington. During the next five years, Dr. Nelson plans to continue his studies of molecular alterations in prostate carcinoma with Dr. Hood as his sponsor and research mentor. The university of Washington has many faculty member engaged in related studies whose advance and guidance will be available. An advisory panel has been assembled to oversee both the applicant's research and academic progress. For the duration of this award, Dr. Nelson will devote at least 75% time and effort towards the research plan as well as participating in national meetings, scientific symposia, and molecular biology course-work. This proposal aims to use high-throughput molecular biological methods to discover the specific genetic differences which are important in the progression of prostate cancer from a patent to an aggressive form, and further to androgen independent growth. High-density arrays of cDNA clones will be constructed to provide a solid-phase archive suitable for a comprehensive analysis of differentially expressed genes. These genetic differences may be used as markers which can aid in diagnosing clinically relevant prostate cancer, and predict the clinical course of a given cancer. Clearly, the management of prostate cancer would be greatly aided by the determination of genetic, biochemical, and epidemiological markers that would discriminate between those cancers best treated by intervention, and those best treated by watchful waiting.
The specific aims are to 1) Identify and quantitate alterations in the transcript levels of genes that associate with phenotypes of prostate cancer progress, 2) characterize the differentially expressed genes correlating with a progressive prostate cancer phenotype. 3) Compile and evaluate a panel of cancer-phenotype associated products for prognostic relevance.
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