Ironing Out the Host-fungal Interaction in Airway Epithelial Cells

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dc.contributor.authorLee, Shernitaen
dc.contributor.committeechairLaubenbacher, Reinhard C.en
dc.contributor.committeechairLawrence, Christopher B.en
dc.contributor.committeememberTorti, Suzy Vivianen
dc.contributor.committeememberHoops, Stefanen
dc.contributor.departmentAnimal and Poultry Sciencesen
dc.date.accessioned2015-10-03T06:00:47Zen
dc.date.available2015-10-03T06:00:47Zen
dc.date.issued2014-04-10en
dc.description.abstractAspergillus fumigatus is a ubiquitous fungus associated with several airway complications and diseases including asthma, allergies, cystic fibrosis, and most commonly invasive aspergillosis. The airway epithelium, a protective barrier, is the first anatomical site to interact with A. fumigatus. Although this host-fungal interaction is often asymptomatic for immunocompetent individuals, for immunocompromised persons, due to a weakened competence of the immune system, they have an increased likelihood of fungal infection. This dissertation aims to investigate the effect of A. fumigatus on the transcriptional response of human airway epithelial cells, focusing on the relationship between innate immunity and iron regulation from the host perspective. The trace element iron is needed by both the fungus and the host for cellular maintenance and survival, but tightly controlled iron regulation in the host is required to prevent oxidative stress and cell death. The research methods in this dissertation employ a systems biology approach, by incorporating mathematical modeling, RNA-seq analysis, and experimental biology techniques to assess the role of airway epithelial cells in the host-fungal interaction. Both the quantitative and qualitative research design allows for characterization of airway epithelial cells and the downstream changes in iron importer genes. This study addresses literature gaps through analysis of the host transcriptome using multiple time points, by performing an extensive evaluation of the effect of cytokines on iron importer genes, and conceptualization of a comprehensive mathematical model of the airway epithelial cell. The major findings suggest the following: 1) airway epithelial cells avidly respond to A. fumigatus through modification of the expression of immune response related genes at different infection stages, 2) during A. fumigatus co-incubation with airway epithelial cells, the iron importers genes respond in strikingly different ways, and 3) cytokines have a significant effect on the increase in expression of an iron importer gene. We illuminated the role of airway epithelial cells in fungal recognition and activation of the immune response in signaling cascades that consequently modify iron importer genes and hope to use this information as a platform to discover potential therapeutic targets.en
dc.description.degreePh. D.en
dc.format.mediumETDen
dc.identifier.othervt_gsexam:2566en
dc.identifier.urihttp://hdl.handle.net/10919/56689en
dc.publisherVirginia Techen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectIron metabolismen
dc.subjectimmune responseen
dc.subjectmathematical modelen
dc.subjecthost-fungal interactionen
dc.subjecttransferrin receptoren
dc.subjectdivalent metal ion transporter 1en
dc.titleIroning Out the Host-fungal Interaction in Airway Epithelial Cellsen
dc.typeDissertationen
thesis.degree.disciplineGenetics, Bioinformatics, and Computational Biologyen
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen
thesis.degree.leveldoctoralen
thesis.degree.namePh. D.en

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