CELLULAR INTERACTIONS IN PULMONARY OXYGEN TOXICITY

肺氧中毒中的细胞相互作用

• 批准号: 6623162
• 负责人: ANBUKILI CHETTY
• 金额: $ 12.8万
• 依托单位: TUFTS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-03-18 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6623162
• 关键词: binding proteins; cell cell interaction; cell proliferation; collagen; cytotoxicity; fibroblasts; growth factor receptors; hyperoxia; insulinlike growth factor; laboratory rat; lung development; lung injury; respiratory epithelium; retinoate; tissue /cell culture

DESCRIPTION (provided by applicant): Cellular Interactions in Pulmonary Oxygen Toxicity in Developing Lung: Candidates background: The candidate has been interested in the pathophysiology of pulmonary diseases in children since her fellowship at Columbia University, NY. Since then she has worked in the field of Asthma and interstitial lung diseases in children. With her experience reinforced with her desire to learn basic research, she was awarded NIH training Grant Fellowship at Case Western Reserve University, Cleveland. Expertise in in vitro co-cultures, cell-cell interaction, cell migration, and hyperoxic exposure of neonatal rat pups was developed. Her stay at New England Medical Center further cultivated this in developing lung. Career goals and objectives: Her goal is to pursue a career as an independent Scientific Investigator, she remains deeply committed to Basic Science research as a way to better understand and treat chronic lung diseases in children. The transition from supervised to independent investigator will require additional years of structured training. Environment: The environment has been excellent with readily available critical review of experimental design and results, and assistance with learning the many new technical procedures required for developing expertise in this area of cell-cell interaction in hyperoxic lung injury. The Advisory Committee consists of authorities in Lung Development and Hyperoxic lung injury in New England Medical Center, Harvard University, Boston Medical Center, and NIDDK, National Institute of Health. Hypothesis: Interaction between Insulin-like growth factor-I (IGF-I) and IGF- I receptor (IGF-IR) is an important regulatory mechanism in hyperoxic lung injury in developing lung. Specific aims: 1. The onset of hyperoxic lung injury in developing lugs is associated with an increase in the expression of IGF-1 in epithelial cells and an increase in the expression of IGF-IR in fibroblasts. 2. IGF-I and IGF-IR interaction regulates epithelial cell- fibroblast communication in hyperoxic lung injury. Induction of fibroblast proliferation and collagen synthesis will be used as evidence of cell-cell interaction using the in vitro and in vivo experiments, and it will be tested by blocking the interaction by various strategies. 3. Retinoic acid decreases the proliferative effect of IGF-I through its action on IGF binding proteins. This mentored work will provide extensive education and technical experience in Molecular Biology and the development of a model of hyperoxic lung injury.

描述（由申请人提供）： 发育中肺氧中毒的细胞相互作用： 候选人背景：候选人对 儿童肺部疾病的病理生理学， 纽约哥伦比亚大学。 从那时起，她一直在哮喘领域工作， 儿童间质性肺病 她的经验得到了加强 她渴望学习基础研究，她被授予国家卫生研究院培训补助金 克利夫兰凯斯西储大学研究员。 专业领域 体外共培养、细胞间相互作用、细胞迁移和高氧 研究了新生大鼠幼仔的暴露情况。 她在新英格兰医疗中心 中心在发育中的肺中进一步培养了这一点。 职业目标和 目标：她的目标是追求职业生涯作为一个独立的科学 作为一名研究员，她仍然致力于基础科学研究， 更好地了解和治疗儿童慢性肺部疾病。 的 从监督调查员过渡到独立调查员将需要更多的 多年的结构化培训。 环境：环境 优秀，对实验设计进行了现成的批判性审查， 结果，并协助学习许多新的技术程序 需要在细胞间相互作用的这一领域发展专门知识， 高氧肺损伤 咨询委员会由龙的当局组成， 哈佛新英格兰医学中心高氧肺损伤的研究进展 大学，波士顿医学中心和NIDDK，国家卫生研究所。 假设：胰岛素样生长因子-I（IGF-I）和IGF-1之间的相互作用 胰岛素样生长因子I受体（IGF-IR）是高氧肺的重要调节机制 发育中的肺损伤。 具体目标：1.高氧肺的发病 发育中的耳损伤与 IGF-1在上皮细胞中的表达和IGF-IR在上皮细胞中表达的增加， 成纤维细胞 2. IGF-I和IGF-IR相互作用调节上皮细胞- 高氧肺损伤中的成纤维细胞通讯 成纤维细胞诱导 增殖和胶原合成将被用作细胞-细胞 使用体外和体内实验的相互作用，并将进行测试 通过各种策略来阻止相互作用。 3.维甲酸减少 IGF-I通过其对IGF结合蛋白的作用的增殖作用。 这项指导工作将提供广泛的教育和技术经验 分子生物学和高氧肺损伤模型的开发。