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

简介(申请人提供)：玛丽·菲利普博士是一名积极进取的高级血液学/肿瘤学研究员，在癌症和免疫学的基础生物学方面具有深厚的背景。她的近期目标是了解血红素在调节T细胞发育和T细胞淋巴瘤发展中的作用。菲利普博士观察到，缺乏FLVCR(一种血红素输出蛋白)的T细胞发育无法在胸腺中完成发育。近年来，人们越来越意识到代谢失调在癌症发生和免疫功能中的作用。虽然血红素的合成和调节是整个细胞代谢的组成部分，但人们对血红素代谢在T细胞发育中的作用知之甚少。菲利普博士将使用小鼠模型来确定血红素水平的调节如何影响正常T细胞的发育和功能，以及T细胞淋巴瘤的发展。菲利普博士将在Janis Abkowitz博士的指导下进行这项研究，Janis Abkowitz博士是血红素和铁运输和造血领域的领先研究员，有成功指导的记录。阿布科维茨实验室为完成这些研究提供了开展分子和免疫学研究所需资源的良好环境。阿布科维茨实验室位于华盛顿大学，在造血学和免疫学领域处于领先地位，拥有许多可用于T细胞生物学研究的资源。在免疫学和其他学科中，有一个特殊的科学家社区来提供建议和合作。菲利普博士还可以使用弗雷德·哈钦森癌症研究中心的教员和设施，该中心是研究和使用造血干细胞移植和免疫疗法治疗癌症的领先者。从长远来看，菲利普博士计划将她的临床培训和治疗白血病和淋巴瘤患者的经验和技能与她强大的基础科学和研究培训结合起来，追求临床科学家的职业生涯。她的职业发展计划提出了一项包括研究、教学课程、参加地方和国家会议的课程，并与阿布科维茨博士和她的科学咨询委员会成员进行有组织的指导，以实现这一目标。 与公共卫生相关：尽管在理解导致癌症的基因变化方面取得了重大进展，但大多数癌症患者最终死于他们的疾病，因为他们的癌细胞对治疗产生了抵抗力。通过研究T细胞发育和T细胞淋巴瘤发生的代谢变化，本研究旨在发现癌症治疗的新靶点，并找到防止癌细胞抵抗治疗的方法。

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.