Stem cell heterogeneity as a driver of cystic fibrosis

Cystic Fibrosis (CF) is a genetic disorder that is characterized by chronic inflammation and build-up of mucus in the lungs. While treatments for the disease do exist, most target the symptoms of the illness and do not focus on the underlying sources of the disease. My work in the McKeon laboratory aims to understand the causative factors of CF by separating patient tissues into individual populations of cells and comparing their behavior to identify potential drivers of the disease. One of the interesting discoveries thus far is that CF patients have unique stem cell populations that, unlike normal airway stem cells, will develop into highly inflammatory or secretory structures - both characteristics of the mature CF tissue. This suggests that aberrant populations of stem cells may be drivers of the disease in ways that are independent of chronic immune system activation. Due to this, it is possible to design treatments that will be more effective against the disease, without impacting the normal function of the immune system. My goal is to characterize the unique behaviors of these diseased cell populations by observing their differentiation in-vivo through mouse xenografts. This process involves harvesting xenografts from treated mice, processing, embedding, sectioning, staining, imaging and characterizing the structures derived from both normal and CF cell lines. Through this comparison, we can observe specific phenotypic differences between normal and CF stem cell populations, which when combined with genetic assays, will brings us much closer to a treatment that is exclusively effective against diseased tissue.