PULMONARY OXYGEN TOXICITY--MECHANISMS AND INTERVENTIONS

申请人是妇产科助理教授，儿科学，和 药理学，在生物医学方面有相当的经验 肺表面活性物质系统和表面活性物质替代治疗。这个 申请者的长期职业目标是发展多学科 研究计划，这将使他能够将基本的兴趣结合在一起 肺细胞生物学与实验性治疗方法 治疗急性肺病。候选人更直接的目标 是为了扩展他实验室目前的细胞生物学专业知识，以及 在分子生物学领域获得更多的实践经验。这个 RCDA将允许申请人减少其目前的教学和 行政责任，以便把全部时间花在 实验室并实现这些目标。申请人所在院校为 支持他的目标并同意候选人对如何实现目标的看法 来实现这些目标。有许多由NIH资助的高级教员在 对肺部研究感兴趣的纽约州立大学世卫组织 与申请者合作并已形成心肺 研究组为沟通提供便利。此外，该大学 正在建设一座新的研究大楼，计划于#年完工 1992-93年度，这将为调查小组提供广泛的空间 有着共同的利益。最后，申请者有广泛的 与罗切斯特大学的合作，并已被邀请 花时间在斯图尔特·霍洛维茨博士的实验室里 接受分子生物学方面的培训。为这一奖项提出的研究 期间涉及到对负责的细胞生物学机制的研究 氧毒性中发生的与表面活性物质相关的变化，以及 确定针对以下目标的治疗干预措施的有效性 在细胞水平上。这些实验使用了最先进的技术， 包括激光流式细胞术，以研究体内氧气的影响 暴露于II型肺泡细胞代谢功能。这些研究将 然后结合实验来确定细胞的功效 定向抗氧化剂治疗。

The applicant is an assistant professor of Gyn/Ob, Pediatrics, and Pharmacology with considerable experience in the biology of the pulmonary surfactant system and in surfactant replacement therapy. The applicant's long term career objective is to develop a multidisciplinary research program which will allow him to combine interests in basic pulmonary cell biology with experimental therapeutic approaches to the treatment of acute lung disease. The candidate's more immediate goals are to expand the current cell biology expertise of his laboratory, and to gain more hands-on experience in the area of molecular biology. The RCDA will allow the applicant to decrease his current teaching and administrative responsibilities in order to spend full time in the laboratory and achieve these goals. The applicant's Institution is supportive of his goals and agree with the candidate's perception of how to achieve them. There are a number of NIH-funded senior faculty at the State University of New York with interests in pulmonary research who collaborate with the applicant and have formed a Cardio-Pulmonary Research Group to facilitate communication. In addition, the University is proceeding with a new research building, slated for completion by 1992-93, which will provide extensive space for groups of investigators with common interest. Finally, the applicant has extensive collaborations with the University of Rochester and has been invited to spend time in the laboratory of Dr. Stuart Horowitz there in order to gain training in molecular biology. The research proposed for this award period involves studies of the cell biological mechanisms responsible for surfactant-related changes which occur in oxygen toxicity, and determination of the efficacy of therapeutic interventions directed at the cellular level. The experiments use state of the art techniques, including laser flow cytometry, to study the effects of in vivo oxygen exposure on type II pneumocyte metabolic function. These studies will then be combined with experiments to determine the efficacy of cell directed anti-oxidant therapy.