PPG -Airway Physiology and Pathophysiology in a Porcine CF Model

PPG - 猪 CF 模型中的气道生理学和病理生理学

• 批准号: 7904983
• 负责人: MICHAEL J. WELSH
• 金额: $ 235.06万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7904983
• 关键词: PPG; Airway; Physiology; Pathophysiology; Porcine

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.

描述（由申请人提供）：CFTR 基因鉴定十八年后，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。进展的一个主要障碍是缺乏除小鼠以外的 CF 动物模型。 CF 小鼠不会出现肺部疾病，而肺部疾病是大多数 CF 发病和死亡的原因。因此，我们破坏了猪的 CFTR 基因，猪的肺部与人类的肺部相似。在该计划中，四名资深且卓有成就的研究人员将抓住独特的机会，使用 CFTR -I- 猪来回答有关 CF 肺病的关键问题。这四个项目将共同探索 CFTR 的缺失如何导致气道上皮和粘膜下腺功能障碍，以及这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 的发现将加速针对患有这种毁灭性疾病的患者的新疗法的开发。