Context dependence of the hippo signaling pathway in the context of pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a devastating chronic lung disease characterized by epithelial injury, subsequent deranged repair and excessive deposition of the extracellular matrix. Reactivation of developmental pathways is emerging as a potential mechanism driving the development of lung fibrosis. One pathway which has been largely unexplored in IPF is the Hippo pathway. The Hippo pathway plays a central role in regulating organ size during development and controls stem/progenitor cell proliferation and differentiation in the adult organism and has been more recently explored in cancer.
Our novel data indicates that a number of Hippo pathway components are decreased in IPF. Interestingly, we have observed that there is a dysregulation of genes known to be downstream of YAP/TAZ (i.e. known downstream targets are both up and down-regulated in IPF). YAP/TAZ cannot directly bind to DNA and must interact with transcription factors to induce changes in gene transcription. The aim of this project is to identify pro-fibrotic YAP/TAZ transcriptional complexes in proximal and distal airway epithelium.

Lung fibrosis is a deadly disease with no available cure. Lung fibrosis can be described as an excessive injury to the lung that stiffens it preventing the barer of the disease from breathing. If you think of the lung as a balloon, lung fibrosis is like crumbling parts of the balloon continuously without stopping. Currently, the only available drugs do not help the patients, they only slow down the disease progression. These patients only survive for a few years once diagnosed. This is because we do not understand the exact causes of the disease. My doctoral studies are focused on identifying specific mechanisms related to lung stiffness in order to find new effective therapies for lung fibrosis.