VEGF and Nitric Oxide in Lung Vascular Development

肺血管发育中的 VEGF 和一氧化氮

• 批准号: 7247192
• 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/7247192
• 关键词: Adolescence; Adult; Adverse effects; Affect; Alveolar; Animals; Biological Preservation; Biology; Blood Circulation; Blood Vessels; Bronchopulmonary Dysplasia; California; Cell Culture Techniques; Cellular biology; Child; Childhood; Chronic Obstructive Airway Disease; Chronic lung disease; Clinical; Clinical Research; Colorado; Coupled; Critical Care; Cultured Cells; Data; Development; Developmental Biology; Disruption; Education; Embryo; Endothelial Cells; Environment; Equipment; Exercise; Exposure to; Fellowship; Gases; Gene Expression; Goals; Grant; Growth; Growth Factor; Growth and Development function; Health Sciences; Hypoxia; In Vitro; Infant; Injury; Investigation; Learning; Los Angeles; Lung; Mentors; Modeling; Molecular; Molecular Biology; Mus; Neonatal; Nitric Oxide; Nitric Oxide Synthase; Oxygen; Pathogenesis; Perinatal; Plants; Predisposition; Premature Birth; Process; Production; Publishing; Pulmonary Emphysema; Pulmonary Hypertension; Pulmonary artery structure; Pulmonology; Rattus; Recovery; Research; Research Personnel; Resources; Risk; Role; Scientist; Series; Severities; Signal Transduction; Stress; Structure; T-Lymphocyte; Techniques; Therapeutic Intervention; Training; Transgenic Organisms; Universities; Vascular Endothelial Growth Factors; Vasodilator Agents; Work; angiogenesis; base; career; critical developmental period; density; experience; fetal; human NOS3 protein; hypoxia neonatorum; in vitro Model; in vivo; infancy; inhaled nitric oxide; injured airway; interest; lung development; lung injury; medical schools; morphometry; mortality; mouse model; neonatal exposure; pediatrician; postnatal; programs; research study; response; response to injury; theories

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的研究员、委员会认证的儿科医生以及儿科肺病学和儿科重症监护委员会资格。他对发育生物学的兴趣始于在加州大学洛杉矶分校接受本科教育期间，在那里他研究了细胞、分子和发育生物学，并进行了植物胚胎基因表达的研究。他在匹兹堡大学医学院继续保持对发育生物学的兴趣，在那里他提出了 γ δ T 细胞的起源和分化模型。在 UHSC 进行进修培训期间，他的兴趣集中在肺血管和肺泡发育。他在出生后肺部生长和发育的整体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。他的近期目标是学习分子和细胞生物学的理论和应用，以了解肺血管生成和肺泡化的机制。他的长期目标是整合整体动物、分子和细胞培养技术，以帮助集中研究肺血管生成在肺泡化中的作用。 Balasubramaniam 博士建议通过体内和体外模型阐明血管生成和肺泡化的相互作用机制，这将帮助我们更好地了解支气管肺发育不良 (BPD) 的发病机制，支气管肺发育不良 (BPD) 是一种早产后的婴儿慢性肺部疾病。在这项提案中，他将使用一种缺乏内皮一氧化氮合酶的转基因小鼠模型，该模型在新生儿轻度缺氧的情况下会出现肺发育不全。在这个模型中，他将结合形态测量、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，发展成为一名独立临床科学家的职业生涯。 UHSC 将提供一个职业发展环境，提供充足的设备和资源，使 Balasubramaniam 博士能够发展成为一名独立调查员。 Steven Abman 博士（导师）在肺部发育的动物和临床研究方面拥有丰富的经验。 Carl White 博士的重点是支气管肺发育不良中氧化性肺损伤的机制。 Kurt Stenmark 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。该顾问委员会的指导加上分子和细胞技术的课程将使他能够推进肺血管生成和肺泡化的研究。此外，Balasubramaniam 博士将继续与 Charles Plopper 博士（加州大学戴维斯分校）合作，学习更复杂的形态分析技术。