Dynamic modelling of human progressive lung fibrosis in a human lung on chip

My research goal is to develop beyond state-of-the-art patient-derived complex cell models of interstitial lung diseases with progressive fibrosis (PF-ILD), amenable to precision medicine and implementation within drug discovery initiatives for better anti-fibrotic or disease modifying drugs. PF-ILD has a fatal outcome, with lung transplantation as only therapeutic option. Recent antifibrotic drugs can only slow down but not halt the disease. The first challenge in understanding and treating human lung fibrotic diseases, is the lack of relevant human models of progressive fibrosis, due to challenges in reproducing persistent inflammation that precedes tissue remodeling and fibrosis. Complex 2D/3D patient-derived cell models provide a solution, as they contain multiple cell types not only providing a better organ mimic, but most importantly allowing to model the complex interplay of the different cell types contributing to persistent inflammation and chronic remodeling. This is important as cues likely not only come from the fibrosis-causing cell i.e. the fibroblast, but also from the airway epithelium, endothelium and immune cells. The second challenge is the idiopathic, multifactorial nature of PF-ILD, which prevents to generate predictive cell models of the disease. As a solution, starting with a pulmonary fibrosis disease with a known genetic origin, e.g. Hermansky-Pudlak syndrome (HPS), can facilitate this process as mutations in HPS are known to lead to impaired surfactant trafficking, alveolar type II dysfunction, epithelial injury, inflammation and tissue scarring.