CELLULAR INTERACTIONS IN PULMONARY OXYGEN TOXICITY

肺氧中毒中的细胞相互作用

• 批准号: 6865426
• 负责人: ANBUKILI CHETTY
• 金额: $ 12.83万
• 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/6865426
• 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)： 发育中肺组织氧中毒过程中的细胞相互作用 应聘者背景：应聘者一直对 儿童肺部疾病的病理生理学研究 哥伦比亚大学，纽约。从那时起，她一直在哮喘领域工作， 儿童间质性肺疾病。随着她的经历得到加强， 由于渴望学习基础研究，她获得了NIH培训补助金 克利夫兰凯斯西储大学的奖学金。在以下方面的专业知识 体外共培养、细胞间相互作用、细胞迁移与高氧 建立新生大鼠仔鼠暴露模型。她在新英格兰医疗中心的住处 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：她的目标是成为一名独立的科学家 作为一名研究员，她仍然坚定地致力于基础科学研究 以更好地了解和治疗儿童慢性肺部疾病。这个 从受监督的调查员过渡到独立调查员将需要额外的 多年的系统训练。环境：环境一直是 具有现成的实验设计和试验设计的批判性审查 结果，并帮助学习许多新的技术程序 发展这一细胞-细胞相互作用领域的专业知识所需的 高氧性肺损伤。咨询委员会由肺脏主管部门组成 哈佛大学新英格兰医学中心的发育与高氧性肺损伤 波士顿医学中心和NIDDK国家健康研究所。 假设：胰岛素样生长因子-I(IGF-I)与IGF-I的相互作用 I型受体(IGF-IR)是高氧性肺损伤的重要调节机制 发育期肺损伤。具体目标：1.高氧性肺的发病 发育中的耳片损伤与基因表达的增加有关 IGF-1在上皮细胞中的表达及IGF-IR的表达增加 成纤维细胞。2.IGF-I和IGF-IR相互作用调节上皮细胞- 高氧性肺损伤中的成纤维细胞通讯。成纤维细胞的诱导 增殖和胶原合成将作为细胞-细胞的证据 使用体外和体内实验进行交互作用，并将进行测试 通过各种策略阻断互动。3.维甲酸减少 胰岛素样生长因子-I对胰岛素样生长因子结合蛋白的促增殖作用。 这项有指导的工作将提供广泛的教育和技术经验 在分子生物学和高氧性肺损伤模型的建立方面。