Human Sample Core

人体样本核心

• 批准号: 8680337
• 负责人: Monica Kraft
• 金额: $ 5.9万
• 依托单位: CEDARS-SINAI MEDICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8680337
• 关键词: Asthma; Biopsy; Biopsy Specimen; Bronchoalveolar Lavage; Bronchoalveolar Lavage Fluid; Bronchoscopy; Bronchoscopy with Bronchoalveolar Lavage; Cataloging; Catalogs; Cell Surface Receptors; Clinical Research; Collaborations; Collection; Data; Databases; Development; Epithelial Cells; Extrinsic asthma; Fibroblasts; Fibrosis; Generations; Hamman-Rich syndrome; Host Defense; Human; Human Resources; Human Subject Research; Hyaluronan; Immunologics; Inflammatory; Instruction; Integration Host Factors; Interleukin-13; Laboratory Personnel; Lung; Lung Inflammation; Lung diseases; Phenotype; Process; Production; Proteins; Protocols documentation; Pulmonary Surfactant-Associated Protein A; Recruitment Activity; Regulation; Research; Research Personnel; Research Project Grants; Safety; Sampling; Signal Transduction; Specimen; Study Subject; System; Transplantation; data management; experience; human subject; laboratory facility; lung injury; macrophage; prevent; programs; receptor; research study; response; sample collection; screening; success; surfactant

The purpose of this proposal is to elucidate the mechanisms by which production of endogenous matrix components in the context of non-infectious lung injury drives unremitting lung inflammation and fibrosis by interacting with cognate receptors leading to the development of an invasive pro-fibrotic fibroblast phenotype. The primary insult of a noninfectious challenge such as that which occurs in idiopathic pulmonary fibrosis or asthma, leads to the generation of endogenous matrix breakdown products that are recognized by a variety of cell surface receptors including TLRs. Critical host defense systems such as surfactant proteins commence to thwart the pro-inflammatory signals produced by the interaction of matrix fragments with cognate receptors. Three inter-related projects are proposed in this application to investigate these mechanisms, two of which employ studies in human subjects with asthma or two which employ studies of subjects with idiopathic pulmonary fibrosis (IPF). Therefore, we propose a Human Sample Core to facilitate the safe and efficient collection of research data and specimens from human subjects and assure adequate phenotyping of subjects. There are several advantages to such a facility. First, consolidating subject recruitment prevents duplication of personnel effort in each research project. Second, standardized subject assessment assures uniformity of experimental data across all projects in this program. Third, assembling an experienced clinical research team helps to maximize subject safety through the course of each research protocol. Finally, the consolidated laboratory facility allows for a uniform subject database and standardized collection, processing and storage of biologic specimens for each project in this program. In aim 1, we will recruit and screen approximately 100 subjects (20/year) with IPF and 150 subjects with asthma (50 mild, 50 severe) and 50 normal subjects to participate in the studies outlined in Projects 1-3. In aim 2, subjects with severe IPF (20/year) receiving lung transplant will undergo bronchoscopy with bronchoalveolar lavage (BAL) in the operating suite for experiments outlined in Projects 1 and 2; 150 subjects (30/year) asthmatic and normal subjects will undergo bronchoscopy with BAL, endobronchial biopsy and brushing to obtain ainway macrophages and epithelial cells, and airway fibroblasts for ex vivo experiments outlined in Projects 2 and 3. In aim 3, lung specimens from 100 subjects with idiopathic pulmonary fibrosis undergoing lung transplant will be obtained for fibroblast invasion studies outlined in Project 1 and specimens obtained from bronchoscopy will be processed for experiments in Projects 2 and 3.

本提案的目的是阐明在非感染性肺损伤的背景下内源性基质组分的产生通过与同源受体相互作用导致侵袭性促纤维化成纤维细胞表型的发展而驱动持续的肺部炎症和纤维化的机制。非感染性攻击的原发性损伤，例如发生在特发性肺纤维化或哮喘中的原发性损伤，导致内源性基质分解产物的产生，所述内源性基质分解产物被多种细胞表面受体（包括TLR）识别。关键的宿主防御系统如表面活性蛋白开始阻碍由基质片段与同源受体的相互作用产生的促炎信号。在本申请中提出了三个相互关联的项目来研究这些机制，其中两个项目采用了对患有哮喘的人类受试者的研究， 患有特发性肺纤维化（IPF）的受试者。因此，我们提出了一个人类样本核心，以促进安全有效地从人类受试者中收集研究数据和标本，并确保受试者的充分表型。这种设施有几个优点。首先，合并受试者招募可以防止每个研究项目中的人员重复工作。二是标准化主体 评估确保了该计划中所有项目的实验数据的一致性。第三，组建一个经验丰富的临床研究团队有助于在每个研究方案的过程中最大限度地提高受试者的安全性。最后，统一的实验室设施可以为该计划中的每个项目提供统一的受试者数据库和标准化的生物标本收集，处理和储存。在目标1中，我们将招募并筛选约100例IPF受试者（20例/年）和150例哮喘受试者（50例轻度，50例 重度）和50名正常受试者参与项目1 - 3中概述的研究。在目标2中，接受肺移植的重度IPF受试者（20例/年）将在手术室接受支气管镜检查和支气管肺泡灌洗（BAL），以进行项目1和2中概述的实验; 150例哮喘受试者（30例/年）和正常受试者将接受支气管镜检查和支气管肺泡灌洗、支气管内活检和刷检，以获得气道 巨噬细胞和上皮细胞以及气道成纤维细胞，用于项目2和3中概述的离体实验。 在目标3中，将获得100例接受肺移植的特发性肺纤维化受试者的肺标本，用于项目1中概述的成纤维细胞侵袭研究，并将处理从支气管镜检查中获得的标本，用于项目2和3中的实验。