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 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 activate innate immune responses and to amplify adaptive immunity. Our research program focuses on elucidating airway epithelial inflammatory responses to 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, COPD, and cystic fibrosis); therefore investigating novel viral mechanisms may provide targets for novel therapies. Recently, this work has progressed to investigate models of trained innate immunity in pulmonary disease.
In collaboration with Drs. Paul Turner and Ben Chan in Ecology and Evolutionary Biology at Yale, Dr. Koff's laboratory has investigated the potential therapeutic role of bacteriophages in lung disease. Bacteriophages (phages) are viruses that infect bacteria. This research has developed a strategy to use phages to target specific bacteria and manipulate surviving bacteria to decrease antibiotic resistance and virulence. These studies include clinical research trials, translational- and laboratory-based projects to investigate phage therapy. D
Asthma; Bacteriophages; Bronchiectasis; Cystic Fibrosis; Immunity, Innate; Influenza, Human; Lung; Viruses; Immunity, Mucosal; Respiratory Mucosa