Basic and Clinical Studies of Cystic Fibrosis

自1997年以来，匹兹堡大学一直有一个囊性纤维化研究中心，尽管其结构和支持机制已经并将继续发生变化。目前的中心收集了超过960万美元的外部赠款和合同，以支持CF相关研究。它由7个部门的39名调查员组成，他们的研究集中在三个主要领域。CF的细胞和分子生物学领域，致力于模型系统中CFTR的研究， 人类气道细胞的研究，由Raymond Frizzell和Joseph Pilewski博士领导，主要通过NIH R 01和囊性纤维化基金会（CFF）赠款以及制药行业合同获得支持。该小组研究CFTR生物发生，运输和调节的机制，CFTR在气道细胞和胰腺生理学中的作用，气道干细胞和上皮钠通道（ENaC），其调节及其与CFTR活性的关系。从这些基础研究中发展而来的治疗方法也在进行中。第二个研究领域，肺部感染和炎症，由Jay Kolls博士领导，专注于人类气道细胞和动物模型中细菌感染的肺部炎症反应，定义这些反应的潜在机制以及如何在治疗上进行修改。这项工作也主要由NIH和CFF赠款， 代表了中心内一个新的、快速发展的领域。第三个也是不断扩大的重点领域是CF的临床研究，由Joseph Pilewski和大卫奥伦斯坦博士领导。该小组正在进行几项临床研究，这些研究来自中心的基础科学倡议，以及CFF治疗发展网络（TON）内的项目;目前主要由CFF赠款支持。拟议的CF研究和翻译核心中心将由Raymond Frizzell博士领导，他还负责CF赞助的 研究开发计划，目前NIH SCOR题为“气道细胞功能的CFTR”，是T32支持的上皮细胞生物学培训计划的共同研究者，并参加了另外两个T32培训计划。Jay Kolls博士和Joseph Pilewski博士将担任该中心的副主任。该中心将由三个核心组成，而不是行政：人类气道细胞生理学（Raymond Frizzell和Joseph Pilewski，共同主任），临床研究/结果（Jay Kolls和Joseph Pilewski，共同主任）和成像（Simon Watkins，主任）。此外，核心中心将开展试点和可行性计划，以鼓励CF研究中的新想法和研究人员。在NTH SCOR应用程序中的过去P/F项目中，100%获得了NIH R 01资助支持，并且所有项目都继续参与CF研究。该中心强调将基础知识转化为应用知识。 治疗学预计的资助期应见证该中心在CF患者中开展的几种新策略的临床试验。

A Cystic Fibrosis Research Center has existed at the University of Pittsburgh since 1997, although its structure and support mechanisms have, and continue to, change. The current center gathers over $9.6M in external grants and contracts in support of CF-related research. It consists of 39 investigators in 7 departments, whose research is focused in three major areas. The area of Cell and Molecular Biology of CF, directed at studies of CFTR in model systems and human airway cells, is led by Drs. Raymond Frizzell and Joseph Pilewski, and is supported largely through NIH R01 and Cystic Fibrosis Foundation (CFF) grants, as well as pharmaceutical industry contracts. This group studies mechanisms of CFTR biogenesis, trafficking and regulation, the role of CFTR in airway cell and pancreatic physiology, airway stem cells, and the epithelial sodium channel (ENaC), its regulation and its relation to the activity of CFTR. Therapeutic approaches evolving from several of these basic studies are being pursued as well. A second research area, Lung Infection and Inflammation, headed by Dr. Jay Kolls, focuses on-the pulmonary inflammatory response to bacterial infection in human airway cell and animal models, defining the underlying mechanisms of these responses and how they can be modified therapeutically. This work is also supported primarily by NIH and CFF grants, and it represents a new and rapidly growing area within the Center. The third and also expanding area of focus is Clinical Research in CF, headed by Drs. Joseph Pilewski and David Orenstein. This group is pursuing several clinical studies that have emerged from the basic science initiatives of the Center, as well as projects within the Therapeutic Development Network (TON) of the CFF; it is supported primarily by CFF grants at present. The proposed CF Research and Translation Core Center will be directed by Dr. Raymond Frizzell, who also directs the CFF-sponsored Research Development Program, a current NIH SCOR entitled 'CFTR in Airway Cell Function', is co-investigator on a T32-supported training program in epithelial cell biology, and participates in two other T32 training programs. Drs. Jay Kolls and Joseph Pilewski will serve as Associate Directors of the Center. The Center will be comprised of three cores other than the Administrative: Human Airway Cell Physiology (Raymond Frizzell and Joseph Pilewski, co-directors), Clinical Studies/Outcomes (Jay Kolls and Joseph Pilewski, co-directors), and Imaging (Simon Watkins, director). In addition, the Core Center will operate a Pilot and Feasibility Program to encourage new ideas and investigators in CF research. Of past P/F projects within the NTH SCOR application, 100% have received NIH R01 grant support and all continue to be involved in CF research. This Center emphasizes the translation of basic knowledge into applied therapeutics. The projected funding period should witness the clinical testing of several novel strategies originating at the Center in CF patients.