PPG -Airway Physiology and Pathophysiology in a Porcine CF Model

描述（由申请人提供）：在CFTR基因鉴定18年后，我们仍然缺乏许多关键问题的答案。围绕气道疾病的发病机制存在争议，目前的治疗方法不足，囊性纤维化（CF）仍然是一种致命的疾病。进展的主要障碍是缺乏除小鼠以外的CF动物模型。CF小鼠不会发生肺部疾病，这是大多数CF发病率和死亡率的原因。因此，我们破坏了猪的CFTR基因，猪的肺与人类的肺相似。在这个项目中，四位资深和非常有成就的研究者将抓住独特的机会，使用CFTR - 1 -猪来回答关于CF肺病的关键问题。这四个项目将共同发现CFTR的缺失如何导致气道上皮和粘膜下腺功能障碍，以及如何导致气道炎症和感染。项目负责人在CF中有着出色的合作记录，在这里他们将注意力集中在一个共同的目标上。他们的研究极具创造性，并得到了提供创新服务和基础设施的五个核心的支持。PPG的发现将加速这种毁灭性疾病患者的新疗法的开发。

DESCRIPTION (provided by applicant): Eighteen years after identification of the CFTR gene we still lack answers to many crucial questions. Controversies surround the pathogenesis of airway disease, current treatments are inadequate, and cystic fibrosis (CF) remains a lethal disease. A major impediment to progress has been lack of a CF animal model other than the mouse. CF mice fail to develop lung disease, the cause of most CF morbidity and mortality. Therefore, we disrupted the CFTR gene in the pig, whose lungs resemble those of humans. In this Program four senior and highly accomplished investigators will seize the unique opportunity to use CFTR -I- pigs to answer key questions about CF lung disease. Together, the four projects will discover how loss of CFTR causes airway epithelial and submucosal gland dysfunction and how that contributes to airway inflammation and infection. The Project Leaders have an outstanding track record of collaboration in CF, and here they sharpen their focus to a common goal. Their research is highly creative and is supported by five cores that provide innovative services and infrastructure. Discoveries from this PPG will accelerate development of novel therapies for patients who suffer from this devastating disease.