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.

Public Health Relevance

Dr. Moore's laboratory has provided seminal studies related to the immunobiology of lung injury, repair and fibrosis both in the context of stem cell transplantation as well as idiopathic forms of disease for over 20 years. This award will support on-going studies to understand how herpesvirus infections promote pneumonitis and fibrosis post-stem cell transplant, to understand how the lung microbiome changes during fibrosis and signals via innate immune receptors, to understand how heparin-binding EGF-like (HB-EGF) growth factor production by myeloid cells drives lung fibrosis and will seek to understand how innate immune signaling can impact lung injury in the setting of influenza and bacterial co-infections.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Unknown (R35)
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Special Emphasis Panel (ZHL1)
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Craig, Matt
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University of Michigan Ann Arbor
Internal Medicine/Medicine
Schools of Medicine
Ann Arbor
United States
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