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)： 位于慢性阻塞性肺病的匹兹堡大学斯科尔分校以我们在慢性阻塞性肺疾病方面的长期研究传统为基础，提出了一个四个项目提案，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。在项目1中，COPD表型异质性的外周标记物；我们的全球假设：COPD是一组可定义的解剖和生理疾病过程，每个过程都有自己的分子和细胞过程，决定了疾病的表现和进展；这将在800名患者中进行测试。在项目2中，COPD的适应性免疫诱导的呼吸道损伤，我们假设适应性免疫过程，由同源识别和对多肽抗原的反应驱动，引起或促成导致COPD进展的气道损伤；这将在人类肺外植体中进行大量测试。在项目3EGR-1：COPD中的细胞凋亡和炎症调节因子中，我们将把人类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)是否在香烟烟雾诱导的慢性阻塞性肺疾病(COPD)的背景下调节细胞凋亡和炎症通路的协调表达。在项目4 COPD气雾剂免疫治疗的临床研究中，我们假设用特定的生物制剂调节COPD受试者识别的免疫反应将消融或改善致病机制，并改变COPD的自然病程。