PI: Erickson, Deborah

Title MIF: A Pro-inflammatory Cytokine as a Novel Target to Reduce Bladder Inflammation
Sponsor: Lexington Biomedical Research Institute
Abstract: Urine Samples will be provided to PI form patient meeting criteria for PBS/IC and subdividing patients into those that show Hunner ulcers verses those that do not show signs of Hunner ulcers upon cystiscopic examination. PI will also prepare results and interpretation, manuscript preparation and design of experiments.

PI: Kyprianou, Natasha

CO-PI: Cibull, Michael
CO-PI: Zhu, Haining
Title: Biomarker Discovery and Mechanistic Studies of Prostate Cancer using Targeted Proteimic Approaches
Sponsor: Army Medical Research and Materiel Command
Abstract: Prostate cancer is a major contributor to cancer mortality in U.S. men, resulting in approximately 30,000 deaths each year. Prostate cancer mortality results from metastasis to the bone and lymph nodes and progression from an androgen-dependent to an androgen-independent disease. No treatment for metastatic prostate cancer is available that effectively increases survival. Proteins on the cell surface are at the frontier that directly interacts with the extracellular environment and encounters signaling factors. Disruption of the expression of cell surface proteins and their post-translational modifications will contribute to imbalance in prostate homeostasis, tumor cell detachment from the extracellular matrix and migration to distant sites. The current understanding of cell surface proteins is incomplete and the purpose of this project is to determine what proteins play which role in prostate cancer progression and metastasis. The long-term objective of this project is to understand the role of cell surface proteins in prostate cancer progression and metastasis. The hypothesis to be tested in this proposal is that cell surface proteins displaying changes in abundances and/or post-translational modifications between benign and malignant prostate cells are likely to be those that are potentially involved in tumor development. Those changes will be identified by comparative studies of benign and malignant prostate cells using systematic and comprehensive approaches (i.e., proteomic approaches). The functional role of such changed proteins in prostate cancer progression and metastasis will be examined in detail. The preliminary proteomic studies have identified a number of cell surface proteins as differentially expressed between benign and malignant prostate cells. Their functional significance in prostate cancer will be determined using a variety of experiments proposed in Specific Aim 1. Encouraged by the initial success of the preliminary studies, we propose to perform more comprehensive analysis of additional types of prostate cells with different tumorigenic behavior. More proteins with relatively subtle changes between benign and malignant prostate cells are expected to be identified. This project is a blend of hypothesis-driven and discovery-driven research and will identify cell surface proteins that are critical to prostate cancer progression and metastasis. Measurement of the expression levels of such proteins in prostate cancer cells, particularly the prostate cancer patient specimens, will potentially develop novel diagnostic/prognostic markers. Further elucidation of their functions will provide invaluable insights into the molecular mechanisms by which localized prostate cancer metastasizes. Such mechanistic understanding will potentially open new avenues for therapeutic intervention of prostate cancer. This project will generate new knowledge of molecular mechanisms involved in prostate cancer as well as provide strong translational significance for the diagnosis and treatment of prostate cancer. The results of this project thus will have direct beneficial impacts on the prostate cancer patients.

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