Author ORCID Identifier
Date of Graduation
12-2020
Document Type
Dissertation (PhD)
Program Affiliation
Biochemistry and Molecular Biology
Degree Name
Doctor of Philosophy (PhD)
Advisor/Committee Chair
Harry Karmouty-Quintana, Ph.D.
Committee Member
Holger Eltzschig, M.D. Ph.D.
Committee Member
Shane Cunha, Ph.D.
Committee Member
Edgar Terry Walters, Ph.D.
Committee Member
Changqing Cynthia Ju, Ph.D.
Abstract
Idiopathic pulmonary fibrosis (IPF) is the most common idiopathic interstitial pneumonia with a median survival time of 2-4 years after diagnosis. The alarming mortality rate is due to the lack of effective treatments. IPF is a chronic disease that is characterized by alveolar destruction due to increasing extracellular matrix deposition that leads to poor lung compliance, impaired gas exchange, and ultimately respiratory failure. Repetitive alveolar epithelial injury is a central process to the underlying pathology with injury to the type II alveolar epithelial cells (AT2) specifically being a key player in the pathogenesis of IPF. Recent studies have shown that recapitulation of developmental genes in AT2 cells is associated with the abnormal epithelial phenotype seen in IPF, however the specific genes and the mechanisms of how they alter epithelial function are poorly understood. The work in this dissertation addresses one such developmental gene, Sine Oculis Homeobox Homolog 1 (Six1), which is a transcription factor that is essential for normal lung morphogenesis in utero that I show to be inappropriately expressed in the AT2 cells in IPF.
Keywords
Idiopathic Pulmonary Fibrosis, Interstitial pulmonary disease, Six1, Eya1, Eya2, MIF, alveolar type II epithelial cells, AT2, IPF, lung fibrosis
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