Core C- Clinical and Translational Core

项目总结/摘要 需要在囊性纤维化（CF）患者和组织中进行测量的实验技术具有 在CF科学中表现出明显的实用性。这些能力使包括重要的 有助于我们了解疾病发病机制的基本方面， 针对CF离子转运缺陷的治疗，以及CFTR调节剂在人类中的评价 科目核心C的目的是为各种CF提供资源、专业知识和支持。 科学家协助项目具有强烈的翻译重点，需要人类受试者的互动， 患者的测量。 为此，核心C履行具体目标中所述的三项主要职能。第一，核心设计 并在人类受试者中进行CFTR活性的体内测量。这包括离子的测量 运输（鼻，下气道和窦电位差），这是CF缺陷的诊断，可以 也可用于监测对改变离子转运途径的CFTR调节剂等试剂的反应， 作为评估CFTR活性的其它手段（例如，汗液氯化物、出汗率等）。第二，核心行为 体内粘液清除的主要措施，利用高影响力的技术，包括一微米 分辨率光学相干断层扫描（μOCT），用于内窥镜探头的体内使用（补充离体 和核心A中的体外成像）;通过Tc 99清除率进行的全肺粘膜纤毛清除率测量;和 流变学和固体含量评估。第三，核心为CF临床的执行提供支持 问题研究临床试验设计和监管支持;生物标本的采集和储存;以及 在婴儿、儿童和成人CF患者中，需要谨慎技术的关键临床结局指标是 包括. 通过采用一套标准的技术、试剂、技术和监管支持以及设备， 中心设施，核心C有助于最大限度地提高测定的一致性，人类受试者参与的效率， 和监管程序。该P30中的许多项目需要CFTR和临床的体内测定 结果，而通过μOCT和其他相关方法在体内测量粘液纤毛运输装置 技术有很高的要求，是我们中心独有的能力。此外，核心驱动成本 通过消除在多个实验室建立相同设备的需要， 生产分析和临床数据存储的规模经济。总体而言，P30核心C进行研究 很好地融入了UAB P30的总体主题，并提供了其他方面无法提供的能力和资源 提供给我们机构和其他机构的各个CF实验室。

PROJECT SUMMARY / ABSTRACT Experimental techniques that require measurements in cystic fibrosis (CF) patients and tissues have demonstrated clear utility in CF science. Such capabilities have enabled advances including important contributions to our understanding of basic aspects of disease pathogenesis, characterization of novel therapeutics directed towards CF ion transport defects, and the evaluation of CFTR modulators in human subjects. The purpose of Core C is to provide resources, expertise, and support to a wide variety of CF scientists to assist projects with a strong translational focus requiring human subject interaction and measurements in patients. To this end, Core C carries out three main functions as delineated in the Specific Aims. First, the Core designs and conducts in vivo measurements of CFTR activity in human subjects. This includes measures of ion transport (nasal, lower airway, and sinus potential difference), which are diagnostic of the CF defect and can be used to monitor the response to agents such as CFTR modulators that alter ion transport pathways, as well as other means of assessing CFTR activity (e.g., sweat chloride, sweat rate, etc.). Second, the Core conducts cardinal measures of mucus clearance in vivo, leveraging high-impact techniques including one micron resolution optical coherence tomography (μOCT) for in vivo use by endoscopic probes (complementing ex vivo and in vitro imaging in Core A); whole-lung mucociliary clearance measurement by Tc99 clearance; and mucus rheology and solid content assessment. And third, the Core provides support for the execution of CF clinical studies. Clinical trial design and regulatory support; collection and storage of biospecimens; and support for key clinical outcome measures that require careful technqiue in infants, children, and adults with CF are included. By employing a standard set of techniques, reagents, technical and regulatory support, and equipment in a centralized facility, Core C helps to maximize consistency of assays, efficiency of human subject involvement, and regulatory processes. Numerous projects within this P30 require in vivo assays of CFTR and clinical outcome, whereas in vivo measurements of the mucociliary transport apparatus by μOCT and other related techniques have a high demand and are capabilities unique to our Center. In addition, the Core drives cost savings by eliminating the need for establishing identical equipment in multiple laboratories and promoting economy-of-scale for production analysis and storage of clinical data. Overall, P30 Core C conducts studies well-integrated into the overall themes of the UAB P30, and provides capabilities and resources not otherwise available to individual CF laboratories at our Institution and beyond.