Thrombocytopoiesis in Hematopoietic Transplantation

描述(由申请人提供)：本提案描述了一项为发展造血干细胞(HSC)移植的学术生涯而开展的培训计划。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。作为医生-科学家指导计划的参与者，PI将通过培训来扩展她的科学技能。骨髓移植项目负责人、造血细胞移植权威克劳迪奥·阿纳塞蒂博士将指导首席研究员的科学发展。此外，一个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。大剂量化疗后长时间的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。佩雷斯博士建议研究体外产生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。在体内，将研究通过趋化因子和/或辅助细胞来改善其功能的方法。对影响周期HSC植入的凋亡机制的研究可能转化为改善体外细胞因子刺激的HSC的归巢、植入和分化以产生巨核细胞。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佳的培育环境，为培训内科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在造血干细胞生物学和移植方面建立成功的独立研究计划的潜力。

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.