Understanding Multiciliated Cell Development and Regulation in Health and Disease
Multiciliated cells differentiated from iPSCs. The cilia projections are stained with alpha tubulin (cyan), pericentrin indicates cell bodies localized at the apical surface (red) and nuclei are counterstained with DAPI (blue). (Image courtesy of the Firth Lab)
Mucociliary clearance is an essential function to prevent chronic airway disease. In the healthy lung, multiple motile cilia beat synchronously to transport inhaled particles and mucus out of the airways. Poor mucociliary clearance is a fundamental feature of many inherited and acquired respiratory diseases, including reduced generation of multiple motile cilia syndrome (RGMC), primary ciliary dyskinesia (PCD), asthma, chronic bronchitis and CF. PCD is a rare (1:15,000) condition, resulting in recurrent respiratory tract infections and progressive lung damage. Supportive care provides the only therapeutic option. In order to develop effective treatments for these diseases characterized by ciliary dysfunction, we need to understand the cellular signaling components that lead to their initiation, development and progression, specifically focusing on multiciliated cells. We are working on:
- dissecting the cellular and molecular pathways influenced by known genetic mutations leading to the development of ciliopathies;
- understanding the role of CFTR in human airway development, particularly the role in multiciliated cell development.