Jaymin Kathiriya, PhD

When the lungs recover from a big injury, normally they can heal themselves. However, this healing ability goes awry in chronic lung diseases like idiopathic pulmonary fibrosis (IPF). Depending on the type and seriousness of the injury, different types of progenitor cells (cells that can differentiate into a specific cell type) are activated and respond by proliferating and differentiating to help the lungs recover. Recent studies from our lab have shown that during disease progression, some of these progenitor cells go through a series of changes that promote disease and scarring. This process eventually leads them to become a type of cell that is often seen in advanced stages of IPF. We will use several state-of-the-art techniques to establish the role of a gene called KRT17 in this process. We will determine whether altering this gene expression will promote normal instead of abnormal disease-causing regeneration. Knowledge gained through this study will advance the development of cell-based therapies for treatments of chronic lung diseases like IPF.

Innovation Award, applied under the Hastings Award

Update: Results from our research suggest that human alveolar epithelial cells (AT2s) are able to change into basal-like cells that are associated with worse outcomes in patients with idiopathic pulmonary fibrosis (IPF). Although animal models have been useful, we developed several new models that let us study how epithelial and mesenchymal cells communicate. This helped us discover new signaling pathways that are directly relevant to human disease. We found that both epithelial and mesenchymal cells work together to trigger abnormal repair processes—not just one cell type alone. To build on these findings, we will use human precision cut lung slices that allow us to capture multiple cell types during lung injury. These studies will help us to better understand how epithelial stem cells respond to signaling cues from multiple different cell types, resulting in the progression of pulmonary fibrosis in the human lung.