Advisor(s)
Stefanie Krick
Committee Member(s)
Camilla Bell
Christian Faul
Jarrod Barnes
Kristopher Genschmer
Megan Kiedrowski
Susan Birket
School
Joint Health Sciences (Interdisciplinary)
Document Type
Dissertation
Department (new version)
Biochemistry and Molecular Genetics
Date of Award
9-11-2025
Abstract
Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene which results in complications in organs such as the lung, pancreas, liver, and intestines. In the lung, defective CFTR results in thick, sticky mucus that causes susceptibility to colonization of opportunistic pathogens such as Pseudomonas aeruginosa (PA), progressive lung damage, and ultimately a decrease in life expectancy in affected individuals depending on severity of disease. Additionally, one of the characteristics of this disease, with and without PA infection, is chronic inflammation. Chronic inflammation has also been associated with accelerated aging which is a hallmark of aging. Another hallmark of aging that is also associated with increases in pro-inflammatory signaling is cellular senescence which has been implicated in CF. Therefore, the likelihood that the CF lung has been impacted by accelerated aging is high. Additionally, fibroblast growth factor (FGF) 23 and FGFR signaling has been found to play a role in inflammation in lung diseases such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). FGF23 signaling has also been implicated to play a role in CF disease pathology as well but the mechanism behind its effect in CF has not been fully elucidated. In this work, we determine the role that FGF signaling plays in the CF bronchial epithelium in the context of cellular senescence and PA infection induced inflammation. We first establish the role FGF23 signaling has on cellular senescence in the CF lung. Then develop a model by which to study prolonged PA infections and subsequently determine the effect of FGF23 signaling on PA infection induced inflammation in the CF bronchial epithelium. Altogether, this work demonstrates the role that FGF signaling plays in the inflamed or senescent CF bronchial epithelial cells, therefore providing evidence for novel potential molecular targets of cellular senescence and inflammation in the CF lung.
ProQuest ID
Recommended Citation
Hirsch, Meghan June, "Investigating The Role Of Fibroblast Growth Factor Signaling In The Cystic Fibrosis Airways" (2025). All ETDs from UAB. 7381.
https://digitalcommons.library.uab.edu/etd-collection/7381
