Human Sample Core

人体样本核心

• 批准号: 8514068
• 负责人: Monica Kraft
• 金额: $ 5.73万
• 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/8514068
• 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.

本研究的目的是阐明在非感染性肺损伤的情况下，内源性基质成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，从而驱动持续的肺部炎症和纤维化的机制。特发性肺纤维化或哮喘等非感染性挑战的主要损害导致内源性基质分解产物的产生，这些产物可被包括tlr在内的多种细胞表面受体识别。关键的宿主防御系统，如表面活性剂蛋白，开始阻止基质片段与同源受体相互作用产生的促炎信号。本申请中提出了三个相互关联的项目来研究这些机制，其中两个采用对哮喘患者的研究，另两个采用对哮喘患者的研究