Basic and Clinical Studies of Cystic Fibrosis

描述(申请人提供)：匹兹堡大学囊性纤维化研究中心目前在8个部门有55名成员，并获得了近1000万美元的外部资助和合同，以支持其囊性纤维化研究工作。这些主要集中在三个主要领域：该中心有一个强大的基础科学部分，解决了囊性纤维化的细胞和分子生物学问题，并得到了NIH、NSF和囊性纤维化基金会(CFF)的资助。这一组的研究人员广泛使用分化的原代人支气管上皮(HBE)进行研究。他们使用生物化学、分子生物学、细胞生物学和电生理学的方法来研究上皮膜上的CFTR和ENaC功能，这些途径如何促进正常的呼吸道功能，它们如何在蛋白质分泌和再循环途径的不同隔室之间运输，以及通道生物发生(校正)或通道活动(增强)的药物操作如何影响HBE功能。肺部感染和炎症的研究主要集中在HBE和动物模型中对细菌感染的肺部炎症反应。这些研究旨在提高我们对CF病发病机制的认识，为临床试验确定生物标志物，并确定抗炎治疗的靶点。临床研究小组将基本发现转化为新的治疗方法。它开发和评估了改善呼吸道药物输送和同位素清除分析的方法，以评估活体内跨壁呼吸道液体的运动，测试针对CF核心缺陷的治疗方法。拟议的研究和翻译核心中心将由雷蒙德·弗里泽尔博士领导，约瑟夫·皮列夫斯基博士将担任副主任。该中心由三个科学核心组成：人体呼吸道细胞和化验(Frizzell，PI)、临床研究/结果(Pilewski，PI)和成像(Watkins，PI)。核心中心将实施一项试点和可行性计划，将新的研究人员引入到CF研究中。该中心强调将基础知识转化为应用治疗学。

DESCRIPTION (provided by applicant): The Cystic Fibrosis Research Center at the University of Pittsburgh currently has 55 members in eight departments and garners nearly $10 M in external grants and contracts to support its CF research efforts. These are focused in three major areas: The Center has a strong basic science component that addresses the Cell and Molecular Biology of CF, and is supported by NIH, NSF and Cystic Fibrosis Foundation (CFF) grants. Investigators in this group make extensive use of differentiated, primary human bronchial epithelia (HBE) for their work. They employ the methods of biochemistry, molecular biology, cell biology and electrophysiology to study CFTR and ENaC functions in epithelial membranes, how these pathways contribute to normal airway function, how they are trafficked between various compartments of the protein secretory and recycling pathways, and how pharmacological manipulation of channel biogenesis (correction) or channel activity (potentiation) influence HBE function. Studies of Lung Infection and Inflammation focus on the pulmonary inflammatory response to bacterial infection in HBE and animal models. These studies aim to improve our understanding of CF disease pathogenesis, define bio-markers for clinical trials, and identify targets for anti-inflammatory therapy. The Clinical Studies group translates basic findings into new therapies. It develops and evaluates methods to improve airway drug delivery and isotopic clearance assays that assess transmural airway liquid movements in vivo, to test therapeutics that target the core defect in CF. The proposed Research and Translational Core Center will be directed by Dr. Raymond Frizzell while Dr. Joseph Pilewski will serve as Associate Director. The Center is comprised of three scientific cores: Human Airway Cell and Assays (Frizzell, PI), Clinical Studies/Outcomes (Pilewski, PI), and Imaging (Watkins, PI). The Core Center will operate a Pilot and Feasibility Program to bring new investigators into CF research. This Center emphasizes the translation of basic knowledge into applied therapeutics.