Immunobiology of Lung Injury and Fibrosis

肺损伤和纤维化的免疫生物学

• 批准号: 10062513
• 负责人: Bethany B. Moore
• 金额: $ 90.13万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-01-21 至 2025-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10062513
• 关键词: Animal Model; Animals; Area; Award; Bacterial Infections; Biological Markers; Clinic; Complication; Data; Disease; Eicosanoids; Etiology; Fibrosis; Growth Factor; Hematopoietic Stem Cell Transplantation; Heparin Binding; Herpesviridae Infections; Human; Immune response; Immune signaling; Immunobiology; Immunologic Receptors; Influenza; Laboratories; Lung; Lung diseases; Malignant Neoplasms; Mediating; Myelogenous; Myeloid Cells; Natural Immunity; Pathogenesis; Pathologic; Pathway interactions; Patients; Process; Production; Proteins; Proteomics; Publishing; Pulmonary Fibrosis; Pulmonary Inflammation; Receptor Signaling; Regulation; Research; Research Personnel; Role; Seminal; Shapes; Signal Transduction; Stem cell transplant; Viral; Virus Diseases; Work; angiogenesis; base; chemokine; co-infection; heparin-binding EGF-like growth factor; injury and repair; interest; lung injury; lung microbiome; microbiome; novel; novel marker; novel therapeutics; programs; therapeutic target; validation studies

The overarching theme for our research program over the past 20 years has been to better understand the etiology and pathogenesis of lung injury, repair and remodeling, with a particular interest in how the immune response shapes pathologic and homeostatic processes in the lung. Our laboratory has contributed seminal studies related to 1) chemokine-mediated angiogenesis in cancer and lung fibrosis, 2) eicosanoid regulation of lung fibrosis, 3) eicosanoid regulation of innate immunity in the setting of hematopoietic stem cell transplantation (HSCT), 4) chemokine regulation of lung fibrosis, 5) fibrocyte functions in lung fibrosis, 6) matricellular protein regulation of lung fibrosis, 7) proteomic, microbiome and other biomarker studies in lung fibrosis, 8) role of viral infections in “idiopathic” lung fibrosis, 9) role of viral infections in mediating pneumonitis and fibrosis post-HSCT and 10) studies of secondary bacterial infection post-influenza. Our work has utilized animal models to carry out mechanistic studies and has utilized patient-derived materials to confirm relevant pathways, identify therapeutic targets and characterize novel biomarkers. Based on our previously published observations and novel preliminary data, our laboratory is broadly focused in 4 main areas. The first is to study innate immune signaling in regulation of secondary bacterial infections post-influenza. The second is to explore interactions between the lung microbiome and innate signaling receptors in the pathogenesis of lung fibrosis. The third is to explore the role of myeloid-specific heparin-binding epidermal-like growth factor (HB-EGF) signaling in regulation of lung fibrosis. The fourth is to further understand the viral etiology and pathogenesis of lung pneumonitis and fibrosis as a complication of HSCT. This outstanding investigator award mechanism will allow us to extend our studies in each of these areas and will allow for mechanistic understanding of the role of immune signaling in the pathogenesis of fibrosis, pneumonitis and lung injury, especially following viral infection. It will also allow our laboratory to complete proof of concept and validation studies needed in both animals and humans to advance new therapies to the clinics for treatment of lung diseases.

在过去的20年里，我们研究计划的首要主题是更好地了解 肺损伤的病因和发病机制，修复和重建，特别是在如何免疫的兴趣 反应形成肺中的病理和稳态过程。我们的实验室为我们的研究 研究涉及：1）癌症和肺纤维化中趋化因子介导的血管生成，2） 肺纤维化，3）类花生酸在造血干细胞背景下对先天免疫的调节 移植（HSCT），4）肺纤维化的趋化因子调节，5）肺纤维化中的纤维细胞功能，6） 肺纤维化的基质细胞蛋白调节，7）肺中的蛋白质组学、微生物组学和其他生物标志物研究 纤维化，8）病毒感染在“特发性”肺纤维化中的作用，9）病毒感染在介导肺炎中的作用 和HSCT后的纤维化和10）流感后继发性细菌感染的研究。我们的工作利用了 动物模型进行机制研究，并利用患者来源的材料，以确认相关的 这些方法可以用于治疗靶点和表征新的生物标志物。根据我们之前发布的 根据我们的观察和新的初步数据，我们的实验室主要集中在4个主要领域。一是研究 先天免疫信号在流感后继发性细菌感染的调节中的作用。二是探索 在肺纤维化的发病机制中，肺微生物组和先天信号受体之间的相互作用。 三是探讨骨髓特异性肝素结合表皮样生长因子（HB-EGF）的作用 调节肺纤维化的信号传导。四是进一步认识病毒病因和发病机制 肺部肺炎和纤维化作为HSCT的并发症。这一杰出调查员奖励机制 将使我们能够扩展我们在这些领域的研究，并将允许机械的理解， 免疫信号在纤维化、肺炎和肺损伤发病机制中的作用，特别是在病毒感染后， 感染它还将使我们的实验室能够完成概念验证和验证研究， 动物和人类，以推进新的治疗方法，以治疗肺部疾病的诊所。