VEGF and Nitric Oxide in Lung Vascular Development

肺血管发育中的 VEGF 和一氧化氮

• 批准号: 6670935
• 负责人: Vivek Balasubramaniam
• 金额: $ 13.07万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 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 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6670935
• 关键词: angiogenesis; bronchopulmonary dysplasia; early experience; enzyme deficiency; genetically modified animals; hypoxia neonatorum; laboratory mouse; lung alveolus; lung development; morphometry; nitric oxide; nitric oxide synthase; nonhuman therapy evaluation; pulmonary circulation; respiratory therapy; stress; tissue /cell culture; vascular endothelial growth factors

DESCRIPTION (provided by applicant): Dr. Vivek Balasubramaniam is a Research Fellow, board certified Pediatrician and board eligible in Pediatric Pulmonology and Pediatric Critical Care at the University of Colorado Health Sciences Center. His interest in developmental biology began during his undergraduate education at the University of California, Los Angeles, where he studied cellular, molecular and developmental Biology and performed research on plant embryonic gene expression. His interest in developmental biology continued at the University of Pittsburgh School of Medicine where he proposed a model for the origin and differentiation of gamma delta T-cells. His interests focused on pulmonary vascular and alveolar development during his fellowship training at UCHSC. He has extensive experience in whole animal studies of postnatal lung growth and development and has developed a focused interest on angiogenesis and alveolarization and the role of growth factors during these processes. His immediate goal is to learn the theories and application of molecular and cell biology to understand the mechanisms that are involved in pulmonary angiogenesis and alveolarization. His long-term goal is to integrate whole animal, molecular and cell culture techniques to help focus independent investigations of the role of pulmonary angiogenesis in alveolarization. Dr. Balasubramaniam proposes to elucidate interactive mechanisms of angiogenesis and alveolarization with in vivo and in vitro models that will help us better understand the pathogenesis of bronchopulmonary dysplasia (BPD), the chronic lung disease of infancy that follows premature birth. In this proposal, he will use a transgeneic mouse model that is deficient in endothelial nitric oxide synthase that develops pulmonary hypoplasia with exposure to mild neonatal hypoxia. In this model, he will combine techniques of morphometry, molecular biology and cell culture to elucidate the mechanisms by which nitric oxide preserves lung angiogenesis and alveolarization. He hopes to combine these different approaches to develop a career as an independent clinician scientist. UCHSC will provide an environment for career development with more than adequate equipment and resources to enable Dr. Balasubramaniam develop into an independent investigator. Dr. Steven Abman (mentor) has broad experience in both animal and clinical studies of pulmonary development. Dr. Carl White's focus has been on the mechanisms of oxidative lung injury in bronchopulmonary dysplasia. Dr. Kurt Stenmark's work has been extensive in the field of pulmonary vascular biology, especially at the cellular and molecular level. Guidance from this advisory board coupled with coursework in molecular and cellular techniques will allow him to advance his studies of pulmonary angiogenesis and alveolarization. In addition, Dr. Balasubramaniam will continue to work with Dr. Charles Plopper (UC Davis) to learn more sophisticated techniques of morphometric analysis.

描述(由申请人提供)：Vivek Balasubramaniam博士是科罗拉多大学健康科学中心儿科肺病学和儿科重症监护方面的研究员、董事会认证儿科医生和董事会成员。他对发育生物学的兴趣始于他在加州大学洛杉矶分校的本科教育期间，他在那里学习细胞、分子和发育生物学，并进行植物胚胎基因表达的研究。他在匹兹堡大学医学院继续对发育生物学感兴趣，在那里他提出了一个伽马三角洲T细胞的起源和分化模型。在UCHSC接受研究员培训期间，他的兴趣主要集中在肺血管和肺泡的发育上。他在出生后肺生长和发育的全动物研究方面拥有丰富的经验，并对血管生成和肺泡化以及生长因子在这些过程中的作用产生了浓厚的兴趣。他的直接目标是学习分子和细胞生物学的理论和应用，以了解涉及肺血管生成和肺泡化的机制。他的长期目标是整合整个动物、分子和细胞培养技术，帮助专注于肺血管生成在肺泡化中的作用的独立研究。Balasubramaniam博士建议用体内和体外模型阐明血管生成和肺泡化的相互作用机制，这将有助于我们更好地理解支气管肺发育不良(BPD)的发病机制，BPD是早产后的婴儿期慢性肺部疾病。在这项提案中，他将使用一种内皮型一氧化氮合酶缺乏的转基因小鼠模型，这种模型会出现肺发育不良，并暴露在轻度新生儿缺氧中。在这个模型中，他将结合形态计量学、分子生物学和细胞培养技术来阐明一氧化氮保护肺血管生成和肺泡化的机制。他希望将这些不同的方法结合起来，发展成为一名独立的临床科学家。UCHSC将为职业发展提供一个环境，拥有足够的设备和资源，使Balasubramaniam博士能够发展成为一名独立的研究员。Steven Abman博士(Mentor)在肺发育的动物和临床研究方面拥有丰富的经验。卡尔·怀特博士的重点是支气管肺发育不良的氧化性肺损伤的机制。斯滕马克博士在肺血管生物学领域开展了广泛的工作，特别是在细胞和分子水平上。来自这个咨询委员会的指导，加上分子和细胞技术方面的课程，将使他能够推进他对肺血管生成和肺泡化的研究。此外，Balasubramaniam博士将继续与加州大学戴维斯分校的Charles Plopper博士合作，学习更复杂的形态测量分析技术。