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The unique role of IkBa in modulating NF-kB activity in the newborn lung.

IkBa 在调节新生肺中 NF-kB 活性方面的独特作用。

基本信息

批准号：
8039962
负责人：
Clyde Jason Wright
金额：
$ 13.39万
依托单位：
CHILDREN'S HOSP OF PHILADELPHIA
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-04-01 至 2011-09-23
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8039962
关键词：
Accounting Advisory Committees Affect Apoptosis Architecture Beer Binding Birth Bronchopulmonary Dysplasia Cell Adhesion Molecules Cell Culture Techniques Cell Survival Cells Characteristics Childhood Chronic lung disease Clinical Clinical Research Clinical Trials Collaborations Complementary DNA Core Facility Cytoplasm DNA Binding Data Defect Development Disease Drug Metabolic Detoxication Embryo Embryonic Development Endothelial Cells Endothelium Environment Exhibits Exposure to Faculty Family Family member Fellowship Gene Expression Gene Expression Regulation Genes Genetic Transcription Hyperoxia Immunohistochemistry Infant Inflammation Inflammatory Injury Intervention Knock-in Mouse Lasers Low Birth Weight Infant Lung Medicine Mentors Messenger RNA Microdissection Modeling Molecular Molecular Biology Molecular Profiling Morbidity - disease rate Mus Mutant Strains Mice N-terminal NF-kappa B Neonatal Neonatology Newborn Animals Newborn Infant Nitric Oxide Nuclear Translocation Oxidants Oxidative Stress Partner in relationship Pathway interactions Pattern Pediatric Hospitals Pediatrics Pennsylvania Perinatal Philadelphia Phosphorylation Physicians Post-Translational Protein Processing Pregnancy Premature Birth Premature Infant Program Development Proteins Public Health Relative (related person)Repression Resources Risk Role Sampling Scientist Serine Signal Pathway Signal Transduction Skin Staging Stress Structure of parenchyma of lung Testing Time Tissues Training Training Programs Tyrosine Universities authority biological adaptation to stress career dimer fetal in vivo inhaled nitric oxide insight lung development lung injury member neonatal lung injury nitration oxidant stress pediatric department postnatal prevent professor programs research study response transcription factor

项目摘要

DESCRIPTION (provided by applicant): This proposal describes the 5-year training program for the development of an academic career in molecular biology and Neonatology. The candidate is in his final year of the Pediatric Scientist Development Program and Neonatology fellowship at the Children's Hospital of Philadelphia (CHOP). This program will expand a body of work in the molecular biology of hyperoxic neonatal lung injury. Phyllis Dennery, MD, a recognized leader in the field of neonatal pulmonary gene regulation in oxidative stress and Professor of Pediatrics at CHOP and the University of Pennsylvania, will supervise the training program. The program will be co-mentored by Michael Beers, MD, an established authority on lung injury and Professor of Medicine at the University of Pennsylvania. To enhance training, an advisory committee consisting of distinguished scientists with expertise in academic medicine, lung injury and NF-kB signaling has been enlisted to provide advice and guidance. Faculty professional development seminars and didactic courses will enhance the educational content of the program. The Division of Neonatology and Department of Pediatrics of CHOP and University of Pennsylvania provide a unique combination of resources, core facilities, intellectual expertise and potential collaborations to support young faculty. This is an ideal training environment to transition to an independent academic career as a physician-scientist. In preterm infants, bronchopulmonary dysplasia (BPD) is common and leads to significant long-term morbidity. Clinical studies have correlated NF-kB activation to an increased risk of developing BPD. Hyperoxia induces NF-kB activation in the neonatal mouse lung. However, the mechanistic pathway leading to this activation and downstream effects are unknown. The central hypothesis of this proposal is that IkB1, a NF-kB inhibitory protein, has unique characteristics that make it essential for regulating hyperoxia-induced NF-kB activation in the newborn lung. The specific aims include: 1) Defining the developmental expression profile of IkB1 in the fetal and neonatal mouse lung, 2) Testing the role of the IkB1 specific atypical pathway of NF-kB activation in modulating lung injury in neonatal mice exposed to hyperoxia, and 3) Determining whether nitric oxide inhibits the atypical pathway of NF-KB activation. By further defining the unique characteristics of IkB1 and its role in modulating hyperoxia-induced NF-kB activation, we hope to identify interventions targeted at protecting preterm infants from BPD.

描述（由申请人提供）：该提案描述了分子生物学和新生儿学学术职业发展的 5 年培训计划。该候选人正处于费城儿童医院 (CHOP) 儿科科学家发展计划和新生儿学奖学金的最后一年。该计划将扩大高氧新生儿肺损伤的分子生物学工作范围。 Phyllis Dennery 医学博士是新生儿肺部氧化应激基因调控领域公认的领导者，也是 CHOP 和宾夕法尼亚大学的儿科教授，她将监督该培训计划。该项目将由医学博士迈克尔·比尔斯 (Michael Beers) 共同指导，他是肺损伤方面的权威，也是宾夕法尼亚大学的医学教授。为了加强培训，我们聘请了一个由在学术医学、肺损伤和 NF-kB 信号传导方面具有专业知识的杰出科学家组成的咨询委员会来提供建议和指导。教师专业发展研讨会和教学课程将增强该计划的教育内容。 CHOP 和宾夕法尼亚大学的新生儿科和儿科提供独特的资源、核心设施、知识专长和潜在合作组合，以支持年轻教师。这是作为一名医师科学家过渡到独立学术职业的理想培训环境。在早产儿中，支气管肺发育不良（BPD）很常见，并导致显着的长期发病率。临床研究已将 NF-kB 激活与患 BPD 的风险增加相关联。高氧诱导新生小鼠肺中 NF-kB 激活。然而，导致这种激活和下游效应的机制途径尚不清楚。该提议的中心假设是 IkB1（一种 NF-kB 抑制蛋白）具有独特的特性，使其对于调节新生肺中高氧诱导的 NF-kB 激活至关重要。具体目标包括：1) 确定 IkB1 在胎儿和新生小鼠肺中的发育表达谱，2) 测试 IkB1 特定的 NF-kB 激活非典型途径在调节暴露于高氧的新生小鼠肺损伤中的作用，以及 3) 确定一氧化氮是否抑制 NF-KB 激活的非典型途径。通过进一步定义 IkB1 的独特特征及其在调节高氧诱导的 NF-kB 激活中的作用，我们希望确定旨在保护早产儿免受 BPD 侵害的干预措施。