Core C- Clinical and Translational Core

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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.