Basic and Clinical Studies of Cystic Fibrosis

描述（由申请人提供）：匹兹堡大学囊性纤维化研究中心目前有8个部门的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CF研究工作。该中心有一个强大的基础科学组成部分，解决CF的细胞和分子生物学问题，并得到NIH， NSF和囊性纤维化基金会（CFF）的资助。本组研究人员广泛使用分化的原代人支气管上皮（HBE）进行研究。他们采用生物化学、分子生物学、细胞生物学和电生理学的方法来研究CFTR和ENaC在上皮膜中的功能，这些途径如何促进正常气道功能，它们如何在蛋白质分泌和循环途径的不同室室之间运输，以及通道生物发生（纠正）或通道活性（增强）的药理学操作如何影响HBE功能。肺部感染与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疾病发病机制的认识，确定临床试验的生物标志物，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。它开发和评估改善气道药物输送和同位素清除测定的方法，以评估体内跨壁气道液体运动，以测试针对CF核心缺陷的治疗方法。拟议的研究和转化核心中心将由Raymond Frizzell博士指导，Joseph Pilewski博士将担任副主任。该中心由三个科学核心组成：人体气道细胞和检测（Frizzell， PI），临床研究/结果（Pilewski， PI）和成像（Watkins， PI）。核心中心将开展试点和可行性项目，为CF研究引入新的研究人员。本中心强调将基础知识转化为应用疗法。

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.