Clinical Subject and Biospecimen Core

临床受试者和生物样本核心

• 批准号: 10636503
• 负责人: Nirav Rati Bhakta
• 金额: $ 38.8万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2028-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10636503
• 关键词: Airway Disease; Applications Grants; Area; Asthma; Biological; Biological Specimen Banks; British Columbia; Bronchoscopy; Cells; Cellular Assay; Chronic Obstructive Pulmonary Disease; Clinical; Clinical Data; Clinical Research; Collection; Cryopreservation; Cytometry; DNA; Data; Databases; Enrollment; Ensure; Epithelial Cells; Epithelium; Functional disorder; Gene Expression Profiling; Goals; Harvest; Human; Image; Immune; Individual; Institutional Review Boards; Link; Lung; Lung diseases; Measures; Messenger RNA; Methods; MicroRNAs; Molecular; Mucous body substance; National Institute of Allergy and Infectious Disease; Participant; Pathology; Pathway interactions; Performance; Process; Proteins; Protocols documentation; RNA; Registries; Regulation; Research; Research Personnel; Resources; Sampling; Secure; Source; Specimen; Structure of parenchyma of lung; System; Tissue Banks; Translational Research; Universities; Work; X-Ray Computed Tomography; airway epithelium; bronchial epithelium; cell bank; clinical phenotype; clinically significant; data submission; experience; experimental study; genomic data; human subject; human tissue; insight; novel; recruit; single-cell RNA sequencing; success; tissue registry

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.

临床核心总结 临床受试者和生物样本处理和分析核心将提供核心资源， 两个项目的每个目标都需要。核心将1）对膨胀的数据进行独特的处理和新颖的分析 来自有或没有哮喘的个体的肺部标本，跨越有或没有粘液塞的区域，2) 招募， 在临床研究中对人类受试者的气道组织进行表征和采样，以及 3) 处理和分发 生物样本和项目数据。 Nirav Bhakta 博士（核心总监）以及由以下人员组成的团队 研究协调员、技术员和程序员分析师，在各方面都有丰富的经验 招募人类受试者进行转化研究方案，并收集和储存高质量的 生物样本。联合研究员蒂莉·哈克特 (Tillie Hackett) 博士领导着一个大型肺组织生物样本库詹姆斯·霍格 (The James Hogg) 不列颠哥伦比亚大学的肺部登记处，并开发了最先进的详细分子分子方法 肺组织的表征。利用这个经验丰富、资源充足的团队的资源， 核心将有三个目标。目标 1 是确定与哮喘和哮喘相关的免疫和气道上皮特征 粘液堵塞肺组织；这包括单细胞、成像质量流式细胞术和基因表达 分析以测量致命性和非致命性哮喘患者肺部的蛋白质、mRNA 和 miRNA， COPD 和无气道疾病的对照。该数据将支持这两个项目。目标2是收集高质量的 来自新支气管镜检查研究的生物样本，使用确保符合标准的系统和方法 联邦和地方法规。这将支持两个需要新鲜收获细胞的项目的研究。目标 3 是提供人类生物样本和数据的专业处理、安全存储和及时分发 这两个项目都协调将数据存储到可公开访问的 NIAID ImmPort 数据库中。此外 提供来自人类捐赠者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供体肺部的上皮刷洗结果，以供后续使用 培养、冷冻保存和单细胞 RNA 测序。 Bhakta 博士和 UCSF 气道临床研究 他进行人体研究的中心在人体受试者招募方面有着成功的记录， 表征和研究支气管镜检查，以及处理、银行、数据库记录和 高质量生物样本和 RNA 的分发，以及分子和细胞检测的安全连接 处理和验证相关临床数据的数据库。 Hackett 博士及其同事进行的研究 来自詹姆斯·霍格肺部登记处的以对供体肺部进行充气并用其进行成像的方法而闻名。 CT 扫描不仅可以比较病理学，还可以比较分子（RNA、DNA、蛋白质）图谱 与健康供体对照相比，患病肺部的情况。鉴于人类研究是不可分割的组成部分 在本次赠款申请中，这一核心对于每个项目的成功实施和建立 其中提出的科学研究的临床意义。