A Novel Stem Cell G Protein-Coupled Receptor

一种新型干细胞G蛋白偶联受体

• 批准号: 7061282
• 负责人: YORIKO SAITO
• 金额: $ 12.42万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7061282
• 关键词: antisense nucleic acid; cell differentiation; cell growth regulation; cell migration; chemokine receptor; genetically modified animals; hematopoiesis; hematopoietic stem cells; laboratory mouse; neutralizing antibody; stem cell transplantation

DESCRIPTION (provided by applicant): The 5-year proposal is designed to prepare the candidate for an academic career in transfusion medicine. Based on clinical training in hematology-oncology, the candidate will gain maturity in scientific skills and experience in the laboratory of Dr. David Scadden at the Massachusetts General Hospital. Dr. Scadden is a well-recognized leader in stem cell research with extensive experience in mentoring trainees. The rich intellectual environment of the AIDS Research center and MGH Cancer Center is ideal for scientific development with opportunity to master a broad range of current techniques in molecular and cellular biology, particularly concepts and methods relating to in vitro and in vivo models of hematopoiesis. The proposal also includes training in transfusion medical scientists in areas of hematology, oncology, immunology and transfusion medicine will provide scientific and career guidance. The proposed research focuses on a novel seven transmembrane G protein-coupled chemokine receptor, SCGPRL. Recent work in the Scadden laboratory showed that SC-GPRI expression is highly restricted to quiescent hematopoietic stem cells (HSC) and ectopic expression of SC-GPR1 confers stem cell phenotype including quiescence and ability to home and engraft in a in vivo mouse transplant model. The proposed project is based on the hypothesis that SC-GPRI expression contributes significantly to mechanisms of HSC quiescence, homing and engraftment. Better defining these mechanisms will lead to improved techniques for HSC manipulation for therapeutic use. The specific aims include: 1. Establishing targeted disruption of SC-GPR1 gene to engineer -/and +/mice, 2. Characterizing the effect of SC-GPRI expression modulation using neutralizing antibody, antisense inhibition and overexpression strategies in addition to the -/- and +/- mice, and 3. Defining the role of SC-GPR1 in HSC homing and engraftment using mouse transplantation models.

描述（由申请人提供）：为期5年的提案旨在为候选人做准备输血医学的学术生涯。 根据血液肿瘤学的临床培训，候选人将在马萨诸塞州综合医院的David Scadden博士实验室中获得科学技能和经验的成熟。 Scadden博士是干细胞研究的公认领导者，在指导学员方面拥有丰富的经验。 艾滋病研究中心和MGH癌症中心的丰富智力环境是科学发展的理想选择，有机会掌握分子和细胞生物学的各种当前技术，尤其是与体外和体内造血模型有关的概念和方法。 该提案还包括在血液学，肿瘤学，免疫学和输血医学领域接受输血医学科学家的培训，将提供科学和职业指导。 拟议的研究重点是一种新型的七个跨膜G蛋白偶联趋化因子受体SCGPRL。 Scadden实验室的最新工作表明，SC-GPRI表达高度限于静止的造血干细胞（HSC）和SC-GPR1的异位表达，赋予干细胞表型，包括静止和在体外小鼠移植模型中进行静止和植入能力。 拟议的项目基于以下假设：SC-GPRI表达对HSC静止，归巢和植入的机制显着贡献。 更好地定义这些机制将改善用于治疗使用的HSC操纵技术。 具体目的包括：1。建立SC-GPR1基因对工程师的靶向破坏 - /和 +/小鼠，2。表征SC-GPRI表达调制的效果，使用中和抗体，反义抑制和过表达策略除了 - // - 和 +/ - 和 +/ - 和 +/ +小鼠外，还使用SC-GPR1 Intraft and Intraft and Intraft and Intraft和3。