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

血红素代谢途径在 T 细胞发育和 T 细胞淋巴瘤基因中的作用

• 批准号: 8293070
• 负责人: Mary Philip
• 金额: $ 16.74万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8293070
• 关键词: Adult; Advisory Committees; Aerobic; Affect; Amino Acids; Anemia; Awareness; B-Cell Lymphomas; Basic Science; Biology; CD8B1 gene; Cancer Immunology Science; Cancer Patient; Cell physiology; Cell surface; Cells; Cellular biology; Citric Acid Cycle; Clinical; Collaborations; Communities; Cytochromes; Development; Development Plans; Discipline; Disease; Educational Curriculum; Environment; Enzymes; Erythroid; Event; Faculty; Failure; Feline Leukemia Virus; Felis catus; Fred Hutchinson Cancer Research Center; Glucose; Glycine; Goals; Hematology; Hematopoiesis; Hematopoietic Stem Cell Transplantation; Hematopoietic stem cells; Heme; Heme Iron; Hemeproteins; Immunologics; Immunology; Immunotherapy; Incidence; Lead; Lymphomagenesis; Malignant Neoplasms; Mature T-Lymphocyte; Mediating; Mentorship; Metabolic; Metabolic Pathway; Metabolism; Modeling; Molecular; Morbidity - disease rate; Mus; Mutation; Nature; Neonatal; Non-Malignant; Normal Cell; Nutrient; Organism; Oxidative Phosphorylation; Oxygen; Pathogenesis; Patients; Phase; Production; Protein Export Pathway; Regulation; Research; Research Personnel; Research Training; Resistance; Resources; Role; Scientist; Staging; Stem cell transplant; Structure; Subgroup; T cell differentiation; T-Cell Development; T-Cell Lymphoma; T-Lymphocyte; Thymus Gland; Time; Training; Universities; Viral Interference; Warburg Effect; Washington; aerobic glycolysis; cancer cell; cancer therapy; career; career development; chemotherapy; experience; heme a; heme receptor; immune function; immunoregulation; improved; insight; leukemia/lymphoma; meetings; member; metabolic abnormality assessment; mortality; mouse model; oncology; oxidative damage; prevent; programs; receptor; reconstitution; research and development; response; skills; succinyl-coenzyme A; therapy resistant; water solubility

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.

玛丽·菲利普博士是一位积极进取的血液/肿瘤高级研究员，在癌症和免疫学基础生物学方面有很强的背景。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。Philip博士观察到，缺乏FLVCR（一种血红素输出蛋白）的发育中的T细胞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展和免疫功能中的作用。虽然血红素的合成和调控是细胞整体代谢的重要组成部分，但对血红素代谢在T细胞发育中的作用知之甚少。Philip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。Philip博士将在Janis Abkowitz博士的指导下进行这项研究，Janis Abkowitz博士是血红素和铁转运和造血领域的领先研究员，具有成功指导的良好记录。Abkowitz实验室为开展分子和免疫学研究提供了良好的环境和必要的资源，以完成这些研究。Abkowitz实验室位于华盛顿大学，该大学在造血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。有一个杰出的免疫学和其他学科的科学家社区提供咨询和合作。他还可以使用Fred Hutchinson癌症研究中心的教师和设施，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导者。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中的技能和见解与她强大的基础科学和研究培训相结合，以追求临床科学家的职业生涯。她的职业发展计划提出了一个研究课程、教学课程、参加地方和国家会议，以及与Abkowitz博士和她的科学咨询委员会成员的结构化指导，以实现这一目标。