Immunobiology of Lung Injury and Fibrosis

在过去的20年里，我们研究计划的首要主题是更好地理解 肺损伤的病因和发病机制、修复和重塑，尤其对免疫如何产生兴趣 反应形成了肺部的病理和内环境平衡过程。我们的实验室已经贡献了 与1)趋化因子介导的肿瘤血管生成和肺纤维化相关的研究，2)二十烷类化合物对肿瘤和肺纤维化的调节 肺纤维化，3)在造血干细胞环境中对先天免疫的二十烷类化合物调节 移植(HSCT)，4)趋化因子对肺纤维化的调节，5)纤维细胞在肺纤维化中的作用，6) 肺纤维化的基质细胞蛋白调控，7)肺蛋白质组、微生物组及其他生物标志物的研究 纤维化，8)病毒感染在特发性肺纤维化中的作用，9)病毒感染在介导性肺炎中的作用 和HSCT后的纤维化，以及流感后继发细菌感染的研究。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证实相关 途径，确定治疗靶点和表征新的生物标记物。基于我们之前发布的 除了观察和新颖的初步数据，我们的实验室主要关注4个领域。第一个是学习 先天免疫信号在调节流感后继发性细菌感染中的作用。二是探索 肺微生物群与先天信号受体在肺纤维化发病机制中的相互作用。 三是探讨髓系特异性肝素结合表皮样生长因子(HB-EGF)的作用 肺纤维化调控中的信号转导。四是进一步了解病毒的病原学和发病机制。 肺肺炎和纤维化是HSCT的并发症。这一杰出的调查员奖励机制 将使我们能够扩展我们在每个领域的研究，并将允许机械性地理解 免疫信号在纤维化、肺炎和肺损伤，尤其是病毒感染后的发病机制中的作用 感染。它还将使我们的实验室能够完成两者所需的概念验证和验证研究 动物和人类将新疗法推向治疗肺部疾病的诊所。

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.