Molecular and Cellular Determinants of Disease Heterogeneity in COPD

COPD 疾病异质性的分子和细胞决定因素

• 批准号: 7564770
• 负责人: FRANK SCIURBA
• 金额: $ 253.81万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-01-12 至 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7564770
• 关键词: Molecular; Cellular; Determinants; Disease; Heterogeneity

DESCRIPTION (provided by applicant): The University of Pittsburgh SCORR in COPD builds upon our long tradition of research in Chronic Obstructive Pulmonary Disease to propose a four project proposal which extends our previous work and our strong collaboration with the University of British Columbia. In project 1 Peripheral Markers of Phenotypic Heterogeneity in COPD; Our global hypothesis: COPD is a heterogeneous group of definable anatomic and physiologic disease processes, each with its own molecular and cellular processes that determine disease manifestation and progression; this will be tested in a well characterized cohort of 800 patients. In project 2 Adaptive Immune-Induced Airway Injury in COPD, we postulate that adaptive immune processes, driven by cognate recognition and responses to peptide antigens, cause or contribute to the airway injuries that result in COPD progression; this will be tested largely in human lung explants. In project 3 EGR-1: Regulator Of Apoptosis And Inflammation in COPD we will translate results from human tissue experiments into mouse models to determine whether early growth response (EGR-1), regulates the coordinated expression of apoptosis and inflammation pathways in the context of cigarette smoke-induced chronic obstructive pulmonary disease (COPD). In project 4 Clinical Investigation Of Aerosol Immunotherapy in COPD we hypothesize that modulation of identified immune responses in COPD subjects with specific biologic agents will ablate or ameliorate pathogenic mechanisms and alter the natural history of COPD.

描述（由申请人提供）： 匹兹堡大学 COPD 领域的 SCORR 基于我们在慢性阻塞性肺疾病研究方面的悠久传统，提出了四个项目提案，扩展了我们之前的工作以及我们与不列颠哥伦比亚大学的密切合作。项目 1：慢性阻塞性肺病表型异质性的外周标志物；我们的总体假设：慢性阻塞性肺病是一组可定义的解剖学和生理学疾病过程，每种疾病过程都有自己的分子和细胞过程，决定疾病的表现和进展；这将在 800 名患者的特征明确的队列中进行测试。在项目 2 慢性阻塞性肺病中的适应性免疫诱发的气道损伤中，我们假设由同源识别和对肽抗原的反应驱动的适应性免疫过程，引起或促成导致慢性阻塞性肺病进展的气道损伤；这将主要在人肺外植体上进行测试。在项目 3 EGR-1：COPD 中细胞凋亡和炎症的调节器中，我们将把人体组织实验的结果转化为小鼠模型，以确定早期生长反应 (EGR-1) 是否在慢性阻塞性肺病的背景下调节细胞凋亡和炎症途径的协调表达。香烟烟雾诱发的慢性阻塞性肺病（COPD）。在项目 4 气溶胶免疫疗法治疗 COPD 的临床研究中，我们假设用特定的生物制剂调节 COPD 受试者中已识别的免疫反应将消除或改善致病机制并改变 COPD 的自然史。