Grant: Doctoral Research Award: Canada Graduate Scholarships

Cystic Fibrosis (CF) is a rare disease affecting over 4300 Canadians caused by a genetic mutation in the gene known as cystic fibrosis transmembrane conductance regulator (CFTR) which codes for the CFTR protein. Dysfunctional CFTR in patients with CF causes progressive, multi-system disease. The most devastating effects occur in the lungs where thick mucus build up can lead to respiratory failure. Most treatments for CF have been focused on treating symptoms, but CFTR modulators introduced over the last decade treat the underlying protein defect responsible for CF. To develop and test these CFTR modulators, in vitro cellular models of CF have been important, but most have been developed from cells of CF patients obtained during lung transplantation. Model systems using more accessible patient tissues are needed to better understand individual responses to CFTR modulator therapies. Using cells from nasal brushings or blood shows promise for more feasible model systems. We hypothesize that in vitro models derived from nasal brushings and induced pluripotent stem (iPS) cells from the blood can be used to predict individual clinical responses to CFTR modulators. To test this hypothesis, my specific objectives are to 1) develop and optimize cell culture models using nasal or iPS cells derived from CF patients, 2) evaluate the function of the CFTR protein before and after modulator therapy using the optimized models, and 3) evaluate the relationship between in vitro and clinical responses to CFTR modulator therapy to establish confidence in the model system. Model systems derived from more accessible patient tissues are especially important for CF patients with rare mutations or patients who fail to show clinical improvements to CFTR modulators. These innovative model systems will allow CF clinicians to advocate for greater CFTR modulator access to reduce health inequities and improve outcomes for all Canadians living with CF.