Clinical Subject and Biospecimen Core

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CLINICAL CORE SUMMARY The Clinical Subject and Biospecimen Processing and Analysis Core will provide a core resource that will be required for each aim of both projects. The core will 1) conduct unique processing and novel analysis of inflated lung specimens from individuals with and without asthma across areas with and without mucus plugs, 2) recruit, characterize, and sample airway tissue from human subjects in a clinical study, and 3) process and distribute biospecimens and data to the projects. Dr. Nirav Bhakta (Core Director), along with a team consisting of a research coordinator, a technician, and a programmer analyst, have considerable experience in all aspects of recruiting human subjects for translational research protocols, and collecting and banking high-quality biospecimens. Co-investigator Dr. Tillie Hackett directs a large lung tissue biospecimen bank, The James Hogg Lung Registry at University of British Columbia, and has developed state of the art methods for detailed molecular characterization of lung tissue. Using the resources of this highly experienced and well-resourced group, the core will have three aims. Aim 1 is to identify immune and airway epithelial features associated with asthma and mucus plugging in banked lung tissue; this includes single-cell, imaging mass cytometry and gene expression profiling to measure proteins, mRNAs, and miRNAs in lungs from individuals with fatal and non-fatal asthma and COPD and controls without airway disease. This data will support both projects. Aim 2 is to collect high quality biospecimens from a new bronchoscopy study using systems and methods which ensure compliance with federal and local regulations. This will support studies in both projects that require freshly harvested cells. Aim 3 is to provide specialized processing, secure storage, and timely distribution of human biospecimens and data to both projects and coordinate deposition of data into the publicly accessible NIAID ImmPort database. In addition to providing very high quality clinical phenotyping and biological specimens from human donors and subjects, this core will process and distribute epithelial brushings from bronchoscopy and from donor lungs for subsequent culture, cryopreservation, and single-cell RNA sequencing. Dr. Bhakta and the UCSF Airway Clinical Research Center in which he conducts human studies have a track record of success in human subjects recruitment, characterization, and research bronchoscopy, and in the processing, banking, database recording and distribution of high-quality biospecimens and RNA, as well as linking of molecular and cellular assays to safely handled and validated databases of associated clinical data. Research conducted by Dr. Hackett and colleagues from The James Hogg Lung Registry is notable for the methods of inflating donor lungs and imaging them with CT scanning to enable the comparison of not only the pathology but also molecular (RNA, DNA, protein) profiles of diseased lungs compared to healthy donor controls. Given that human studies are an integral component of this grant application, this core will be critical for the successful performance of each project and for establishing the clinical significance of the scientific studies proposed within them.