Acute and chronic forms of lung disease remain major health care burdens and are expected to increase with an aging population. Altering the course of this intractable disease will require innovative and novel approaches to understand the underlying mechanisms of disease and develop therapeutic alternatives with a realistic path to clinical translation. The regenerative medicine landscape for the lung and trachea can be categorized into the following: (1) Cell-based therapeutic approaches for attenuation and/or abrogation of disease; (2) ex vivo cell culture systems as platforms for disease modeling and therapeutics; and (3) tissue regeneration for replacement of damaged airway tissue. Importantly, all of these approaches require practical numbers of functional therapeutic cells. We also need a thorough understanding of the cells and their function in their native and applied microenvironments. My research program is focused on the application of pluripotent stem cell sources in ‘Airway Regeneration’, balancing translational and exploratory approaches with the goal to better understand cell-microenvironment interactions. We seek to use the acquired information to develop and utilize physiologically relevant ex vivo platforms and thus engineer clinically applicable therapeutic strategies.