This proposal outlines an intensive 5 year training program designed to prepare the principal investigator for a career as a physician scientist in tumor immunology. The candidate is currently a third year hematology fellow with 1.5 years of basic science experience in the lab of Dr. Jenny Ting at the University of North Carolina Chapel Hill. This award will enable the investigator to achieve scientific independence by providing a dedicated period of bench research in a comprehensive educational environment. At the end of the term, he will have acquired the necessary technical skills as well as scientific rigor to contribute to the fields of tumor immunology as an academic physician. The applicant's research in Dr. Ting's lab focuses on the migration and function of murine dendritic cells (DCs).
The aims of this work are (1) to compare the migration of immature and mature DCs after subcutaneous and intravenous injection, (2) to describe the impact of cancer on DC migration, and (3) to explore the potential therapeutic benefit of increasing DC migration to the tumor by genetic manipulation. This will be done by injecting DCs cultured from the bone marrow of transgenic mice expressing enhanced green fluorescent protein (EGFP). These cells will be identified in vivo using micro-fluoroscopy and flow cytometry and isolated with cell sorting. The functional changes induced by migration from injection site will then be assessed. This inventive strategy will lead to a better understanding of activation and maturation of DCs in vivo and novel approaches to immunotherapy. The applicant's work will be reviewed regularly by Drs. Jenny Ting, Jon Serody, and Beverly Mitchell. Dr. Ting will serve as the primary laboratory mentor. Her lab is well funded and committed to applying cellular and molecular approaches to cancer and transplantation. Dr. Serody has extensive basic science experience with DCs and is currently leading UNC's effort to develop DC vaccines. Dr. Mitchell is chief of the hematology/oncology division at UNC and is nationally recognized in the field of hematology as a clinician scientist. All have extensive experience in developing the careers o f young scientists. This work has the support of the Lineberger Comprehensive Cancer Center which has made accessible its core facilities.
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