TRANSFERRIN RECEPTOR AND ERYTHROPOIESIS

候选人是医学博士。完成了完整的医学训练 包括临床血液学/肿瘤学奖学金，现在正在密集 追求基础研究，最终目标是成为一名 独立调查员 这项研究将在 一家大型教学医院的血液科。 实验室组 专注于红细胞发育，并在分子生物学方面拥有专业知识 和转基因技术。该研究项目研究红细胞 分化与发展。缺铁是导致 世界范围内的贫血，保守估计超过5亿人 受影响;然而，尽管这种频率，其病理生理学 不完全理解。 该项目概述的重点是 铁在调节红细胞分化和发展的目标 铁对正常红细胞生成的阻碍 缺陷 转铁蛋白受体将被基因操纵， 小鼠胚胎干细胞 这些细胞将被注射到小鼠体内 胚泡并培育至纯合性，以允许在体内研究 转铁蛋白循环如果纯合子小鼠是不能存活的嵌合小鼠， 使用胚胎干细胞产生，其中两个拷贝的 转铁蛋白受体已经改变。 实验也在计划之中 利用体外红系分化技术， 基因改造的胚胎干细胞了解到的信息将导致 增加对铁阻止红细胞生成的理解， 不足之处，并最终制定新的治疗策略 治疗缺铁和铁过量

The candidate is an M.D. who has completed full medical training including clinical hematology/oncology fellowship and is now intensively pursuing basic research with the ultimate goal of a career as an independent investigator. The research will be carried out in the hematology division of a major teaching hospital. The laboratory group focuses on erythroid development, and has expertise in molecular biology and transgenic technology. The research project investigates red cell differentiation and development. Iron deficiency is the leading cause of anemia world wide, with conservative estimates of over 0.5 billion people affected; however, despite this frequency its pathophysiology is incompletely understood. The project outlined focuses on the role of iron in regulating red cell differentiation and development with the goal of increasing understanding of the block to normal erythropoiesis in iron deficiency. The transferrin receptor will be genetically manipulated in murine embryonic stem cells. These cells will be injected into mouse blastocysts and bred to homozygosity to allow in vivo study of the transferrin cycle. If homozygous mice are non-viable chimeric mice will be generated using embryonic stem cells in which both copies of the transferrin receptor have been altered. Experiments are also planned utilizing the technique of in vitro erythroid differentiation of these genetically altered embryonic stem cells. Information learned will lead to increased understanding of the block to red cell production in iron deficiency, and ultimately to the development of new treatment strategies for iron deficiency and iron overload.