The Role of Heme Metabolic Pathways in T Cell Development and T Cell Lymphomagene

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DESCRIPTION (provided by applicant): Dr. Mary Philip is a motivated senior hematology/oncology fellow with a strong background in the basic biology of cancer and immunology. Her immediate goals are to understand the role of heme in regulating T cell development and T cell lymphoma development. Dr. Philip has observed that developing T cells that lack FLVCR, a heme export protein, fail to complete development in the thymus. In recent years there has been growing awareness of the role of metabolic dysregulation in cancer development and immune function. Though heme synthesis and regulation are integral parts of overall cellular metabolism, little is known about the role of heme metabolism in T cell development. Dr. Philip will use mouse models to determine how modulation of heme levels affects the development and function of normal T cells as well as the development of T cell lymphomas. Dr. Philip will carry out this research under the guidance of Dr. Janis Abkowitz, a leading researcher in the field of heme and iron transport and hematopoiesis with a proven track record of successful mentorship. The Abkowitz lab provides an excellent environment with the necessary resources to carry out the molecular and immunologic studies to complete these studies. The Abkowitz lab is located at the University of Washington, a leader in the fields of hematopoiesis and immunology with many resources available for the study of T cell biology. There is an exceptional community of scientists in immunology and other disciplines to provide advice and collaboration. Dr. Philip also has access to the faculty and facilities of the Fred Hutchinson Cancer Research Center, the leader in the study and use of hematopoietic stem cell transplantation and immunotherapy to treat cancers. In the long-term, Dr. Philip plans to combine the skills and insights from her clinical training and experience treating patients with leukemia and lymphoma with her strong basic science and research training to pursue a career as a clinician-scientist. Her career development plan proposes a curriculum of research, didactic coursework, participation in local and national meetings, and structured mentorship with Dr. Abkowitz and the members of her Scientific Advisory Committee to achieve this goal. PUBLIC HEALTH RELEVANCE: Though major advances have been made in understanding the genetic changes that lead to cancer, most cancer patients eventually die from their disease because their cancer cells become resistant to therapy. By studying the metabolic changes that underlie T cell development and T cell lymphoma development, this research aims to uncover new targets for cancer therapy and to find ways to prevent cancer cells from resisting treatment.