Background Research and Focus

The airways are continuously exposed to pathogens, allergens, toxins, and environmental contaminants. In addition to its role as a physical barrier, the airway epithelial surface represents a “battleground,” where the host intercepts signals from pathogens (e.g., viruses and bacteria) and activates epithelial defenses to prevent infection. The defensive roles of the airway epithelium are crucial; the epithelium activates innate defense mechanisms and recruits inflammatory and immune cells to amplify innate immune responses, and to influence adaptive immunity.

Our research program focuses on elucidating airway epithelial signaling pathways that are important for inflammatory responses to pathogens. This work focuses on two areas:

• Viral infection: utilizing both in vitro and ex vivo airway epithelial cell cultures and murine models, we have found novel signaling pathways, which regulate viral infection. Currently, there are only limited therapies available to treat viral exacerbations of chronic airway diseases (e.g., asthma and COPD); therefore, investigating novel viral mechanisms may provide targets for novel therapies.
• Cystic Fibrosis: because I care for adult patients with cystic fibrosis, I have a commitment to investigate mechanisms of this disease. Exaggerated airway epithelial inflammation is a hallmark of cystic fibrosis, and to date there are limited anti-inflammatory therapies that are clinically efficacious. Historically, the study of viruses has provided important insights into basic cell function, and while studying epithelial responses to viral infection, we discovered an airway epithelial signaling pathway with relevance to CF inflammation. Therefore, in this project we will utilize the cellular mechanisms discovered by investigating airway epithelial viral infection to target molecules in cystic fibrosis airway epithelium and lung.