Thrombocytopoiesis in Hematopoietic Transplantation

造血移植中的血小板生成

• 批准号: 7436317
• 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/7436317
• 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; Cellular biology; 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

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）：该提案描述了造血干细胞（HSC）移植学术生涯发​​展的培训计划。首席研究员 (PI) 是 H. Lee Moffitt 癌症中心骨髓移植项目的初级教员。 PI 将通过参加医师-科学家指导计划的培训来扩展她的科学技能。骨髓移植项目负责人、造血细胞移植领域的权威 Claudio Anasetti 博士将指导首席研究员的科学发展。此外，由备受尊敬的医学科学家组成的咨询委员会将提供科学和职业建议。高剂量化疗后长期血小板减少是与发病率和死亡率增加相关的问题。拟议的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 博士提议研究体外生成的巨核细胞在人类巨核细胞生成的异种移植模型中的血小板生成作用。将研究利用趋化因子和/或辅助细胞改善其功能的体内方法。将讨论影响循环HSC植入的细胞凋亡机制的研究，该机制可能转化为改善体外细胞因子刺激的HSC以产生巨核细胞的归巢、植入和分化。此外，还将研究可能调节巨核细胞生成和参与血小板重建的基因的分子研究。莫菲特癌症中心拥有极其培育的环境，为培训医师科学家提供了理想的环境。科学家、医生/科学家和临床研究人员之间的互动最大限度地发挥了 PI 的潜力，以建立成功的造血干细胞生物学和移植独立研究计划。