This application requests renewal of a grant to provide advanced, state of the art, post-doctoral training in three active and closely related fields: angiogenesis, inflammation and tumor cell invasion/metastasis. These areas of emphasis were selected because of their increasing relevance for understanding a growing list of important human diseases including atherosclerosis, cancer and chronic inflammatory syndromes. Extensive public and private resources are being directed towards the identification of pharmacological agents suitable for the suppression and/or stimulation of blood vessel growth, and many clinical trials are now underway to evaluate specific modulators of vessel growth as potential therapeutics. Moreover, the cells and mediators found in immunological and inflammatory responses can significantly enhance, or, in some instances, suppress angiogenesls. Tumor invasion and metastasis are characterized by both angiogenesis and inflammation and all three processes share common features such as cell migration and division, stroma generation and intracellular signaling. Despite a clear and growing need, few opportunities now exist for providing broad, in depth, and interdisciplinary training for individuals to investigate productively the complex and interrelated processes that regulate normal and pathological vascular growth, the inflammatory response and tumor cell invasion and metastasis. We propose to train five postdoctoral fellows per year selected from applicants who have completed Ph.D., M.D., or M.D./Ph.D. degrees. Training is based primarily in the Division of Experimental Pathology at Beth Israel Deaconess Medical Center. The Division comprises 25 interactive faculty members with expertise in angiogenesis, tumor cell invasion/metastasis and inflammation. Active ongoing collaborations between the training program's faculty and the clinical faculty in Surgical Pathology offer access to clinical specimens that provide important material for training and research. Principal areas of training include: (1) regulation of angiogenesis in cancer; (2) regulation of angiogenesis in non-neoplastic disorders; (3) molecular regulation of inflammation; (4) angiogenic growth factors; (5) inhibitors of vessel growth; (6) intracellular signaling in angiogenesis and inflammation and (7) tumor cell invasion and metastasis.
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