Thrombocytopoiesis in Hematopoietic Transplantation

造血移植中的血小板生成

• 批准号: 7647941
• 负责人: LIA ELENA PEREZ
• 金额: $ 12.74万
• 依托单位: H. LEE MOFFITT CANCER CTR & RES INST
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-04 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7647941
• 关键词: Ablation; Address; Advisory Committees; Affect; Antigen-Presenting Cells; Apoptosis; Apoptotic; Blood; Blood Platelets; Bone Marrow Transplantation; CXCR4 gene; Cancer Center; Cell Cycle; Cell Transplantation; Cells; Clinical Investigator; Data; Defect; Development; Disease; Engraftment; Environment; Evaluation; Exposure to; Faculty; Genes; Hematologic Neoplasms; Hematopoietic; Hematopoietic Stem Cell Transplantation; Hematopoietic stem cells; High Dose Chemotherapy; Homeostasis; Homing; Human; Immune; In Vitro; Marrow; Mediating; Medical; Megakaryocytes; Mentors; Mentorship; Mesenchymal Stem Cells; Modeling; Molecular; Morbidity - disease rate; Mus; Non obese; Non-Malignant; Participant; Pathway interactions; Physicians; Play; Population; Principal Investigator; Program Development; Radiation; Recovery; Research; Role; SCID Mice; Scientist; Stem cells; Stress; TNFRSF6 gene; Thrombocytopenia; Thrombopoiesis; Training; Training Programs; Translating; Transplantation; Xenograft procedure; authority; career; chemokine; chemotherapy; cytokine; design; diabetic; human INPPL1 protein; improved; in vivo; inhibitor/antagonist; mortality; novel strategies; pre-clinical; progenitor; programs; receptor; receptor expression; reconstitution; skills; stem cell biology

DESCRIPTION (provided by applicant): This proposal describes a training program for the development of an academic career in hematopoietic stem cell (HSC) transplantation. The principal investigator (PI) is a junior faculty of the Bone Marrow Transplant Program at H. Lee Moffitt Cancer Center. The PI will expand her scientific skills through training as participant of a Physician-Scientist mentorship program. Dr. Claudio Anasetti, Chief of the Bone Marrow Transplantation Program and an authority in hematopoietic cell transplantation, will mentor the principal investigator's scientific development. In addition, an advisory committee of highly regarded medical scientists will provide scientific and career advice. Prolonged thrombocytopenia after high dose chemotherapy is a problem associated with increased morbidity and mortality. The proposed research will provide preclinical data on novel strategies to improve platelet reconstitution post transplant. Dr. Perez proposes to study the thrombopoietic role of in vitro generated megakaryocytes in a xenotransplantation model for human megakaryocytopoiesis. In vivo approaches to improve their function with chemokines and/or accessory cells will be studied. Research on apoptotic mechanism affecting engraftment of cycling HSC that may translate on improved homing, engraftment and differentiation of in vitro cytokine stimulated HSC to generate megakaryocytes will be addressed. In addition, molecular studies of genes that may regulate megakaryocytopoiesis and participate in platelet recontitution will be studied. Moffitt Cancer Center has an extremely nurturing environment and provides an ideal setting for training physician scientists. Interactions between scientists, physician/scientists and clinical investigators maximizes the potential of the PI to establish a successful independent research program on hematopoietic stem cell biology and transplantation.

描述（由申请人提供）：本提案描述了造血干细胞（HSC）移植学术生涯发展的培训计划。主要研究者（PI）是H.李莫菲特癌症中心。PI将通过培训作为物理学家-科学家导师计划的参与者来扩展她的科学技能。Claudio Anasetti博士是骨髓移植项目的负责人，也是造血细胞移植的权威，他将指导主要研究者的科学发展。此外，一个由德高望重的医学科学家组成的咨询委员会将提供科学和职业建议。大剂量化疗后持续性血小板减少是一个与发病率和死亡率增加相关的问题。这项研究将为改善移植后血小板重建的新策略提供临床前数据。Perez博士建议在异种移植模型中研究体外生成的巨核细胞在人类巨核细胞生成中的血小板生成作用。将研究用趋化因子和/或辅助细胞改善其功能的体内方法。影响周期性HSC植入的凋亡机制的研究可能会转化为体外细胞因子刺激的HSC产生巨核细胞的归巢，植入和分化的改善。此外，还将对可能调节巨核细胞生成和参与血小板重建的基因进行分子研究。莫菲特癌症中心有一个非常有利的环境，并提供了一个理想的环境，为培训医生科学家。科学家、医生/科学家和临床研究者之间的互动最大限度地发挥了PI的潜力，以建立一个成功的造血干细胞生物学和移植独立研究项目。