University of Southern California

Ryan (Firth) Lab

USC Stem Cell

Lab Overview

One of the major limitations to studying human lung disease is limited access to primary airway epithelial cells and poor recapitulation of human disease in rodent models, leading to fewer therapies making it to the clinic. To progress toward new therapeutics and eventually cures, it is imperative to study the human lung, including cells from the proximal conducting and distal gas exchange regions across a diverse spectrum of lung disease patients. My research program is focused on the development and utilization of iPSC models of human lung disease to overcome this critical lack of model systems that closely reflect disease pathogenesis as it occurs in humans. The Ryan laboratory focuses on applying in vitro, in vivo, iPSC and 3-D spheroid models including primary lung epithelial cells and state-of-the-art gene editing technologies to a) model and study mechanisms of lung development and disease, and b) investigate approaches for tissue regeneration and stem cell-mediated repair of the airway epithelium. To support this highly innovative program, we have established critical collaborations with clinicians, engineers, large animal research groups and bioinformaticians both within USC and around the world. Our long-term goal is to fully understand specification of specialized airway epithelial cell types from stem and progenitor cells in the human lung in the context of injury, regeneration and disease pathogenesis. Our primary research focus is on rare lung diseases where human samples are particularly difficult to obtain or from end stage disease, namely cystic fibrosis (CF) and primary ciliary dyskinesia (PCD).

iPSC colony derived from skin fibroblasts of a patient with cystic fibrosis. The colony is stained with pluripotency markers Lin28 (red) and Sox2 (green), and DAPI (blue) indicates nuclei. (Image courtesy of the Firth Lab)
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)
Club cells differentiated from iPSCs. Club cell secretory protein is indicated in green. Tight junctions between epithelial cells are stained with occluding (ZO-1 in red) and the nuclei are counterstained with DAPI (blue). (Image courtesy of the Firth Lab)