Immunobiology of Lung Injury and Fibrosis

肺损伤和纤维化的免疫生物学

• 批准号: 10523118
• 负责人: Bethany B. Moore
• 金额: $ 85.71万
• 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/10523118
• 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; chemokine; co-infection; heparin-binding EGF-like growth factor; interest; lung injury; lung microbiome; microbiome; novel; novel marker; novel therapeutics; pneumonitis and fibrosis; programs; repaired; 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.

过去20年来我们研究计划的总体主题是更好地了解 肺损伤，修复和重塑的病因和发病机理，对免疫的方式特别感兴趣 反应塑造肺中的病理和稳态过程。我们的实验室已经贡献了半个 与1）趋化因子介导的癌症和肺纤维化的血管生成有关的研究，2）类类调节 肺纤维化，3）在造血干细胞环境中对先天性免疫的eicosanoid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，7）蛋白质组学，微生物组和其他生物标志物研究的母细胞蛋白质调节 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 HSCT后纤维化和纤维化10）研究后感染后期细​​菌。我们的工作已经使用了 动物模型进行机械研究，并利用患者衍生的材料来确认相关 途径，确定治疗靶标并表征新型生物标志物。根据我们先前出版的 观察结果和新的初步数据，我们的实验室广泛集中在4个主要领域。首先是学习 在调节次生细菌感染后，先天性免疫信号传导。第二个是探索 肺纤维化发病机理中肺微生物组与先天信号受体之间的相互作用。 第三个是探索髓样特异性肝素结合表皮样生长因子（HB-EGF）的作用 肺纤维化调节中的信号传导。第四是进一步了解病毒病因和发病机理 肺部肺炎和纤维化是HSCT的并发症。这种杰出的调查员奖励机制 将使我们能够在每个领域中扩展研究，并允许对 免疫信号在纤维化，肺炎和肺损伤的发病机理中的作用，尤其是病毒 感染。这还将允许我们的实验室完成两者所需的概念和验证研究证明 动物和人类将新疗法推向诊所治疗肺部疾病。