Clinical Subject and Biospecimen Core

临床核心总结 临床受试者和生物标本处理和分析核心将提供一个核心资源， 这两个项目的每个目标都需要。核心将1）进行独特的处理和新颖的分析膨胀 来自患有和不患有哮喘的个体的肺样本，横跨具有和不具有粘液栓的区域，2）招募， 在临床研究中表征和采样来自人类受试者的气道组织，以及3）处理和分配 生物标本和数据的项目。Nirav Bhakta博士（核心总监），沿着， 研究协调员，技术员和程序员分析师，在各个方面都有相当丰富的经验， 为转化研究方案招募人类受试者，并收集和储存高质量的 生物标本合作研究员Tillie Hackett博士指导一个大型肺组织生物标本库，James Hogg 肺登记处在不列颠哥伦比亚省，并已开发出最先进的方法，详细的分子 肺组织的表征。利用这个经验丰富、资源丰富的小组的资源， 核心将有三个目标。目的1是确定与哮喘相关的免疫和气道上皮特征， 粘液堵塞在库存肺组织中;这包括单细胞、成像质量细胞术和基因表达 分析以测量来自患有致命性和非致命性哮喘的个体的肺中的蛋白质、mRNA和miRNA， COPD和无气道疾病的对照组。这些数据将支持这两个项目。目标2：收集高质量的 来自一项新的支气管镜检查研究的生物标本，使用的系统和方法可确保符合 联邦和地方法规。这将支持两个项目中需要新鲜收获细胞的研究。目标3 提供专门处理、安全存储和及时分发人类生物标本和数据， 这两个项目，并协调数据存入公众可访问的NIAID ImmPort数据库。此外 提供来自人类供体和受试者的非常高质量的临床表型和生物样本， 该核心将处理和分配来自支气管镜检查和来自供体肺的上皮刷， 培养、冷冻保存和单细胞RNA测序。Bhakta博士和UCSF气道临床研究 他进行人类研究的中心在人类受试者招募方面有成功的记录， 表征和研究支气管镜检查，并在处理，银行，数据库记录和 高质量生物标本和RNA的分发，以及分子和细胞检测的连接， 处理和验证相关临床数据的数据库。哈克特博士及其同事进行的研究 来自James Hogg肺登记处的方法是值得注意的，其方法是使供体肺膨胀并用 CT扫描不仅可以比较病理学特征，还可以比较分子（RNA、DNA、蛋白质）特征 与健康供体对照组相比，鉴于人体研究是 这个补助金的申请，这一核心将是至关重要的，每个项目的成功执行，并建立 其中提出的科学研究的临床意义。

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.