Katherine Halee
Research Mentor: Thomas Sisson
Mentor Department: Internal Medicine, Medicine
Author(s): Katherine Halee, Lisa Leung, Madison Matos, Thomas Sisson
Session: Session 2 (10:00 AM – 10:50 AM)
Presentation Type: Poster 123
Abstract
Idiopathic pulmonary fibrosis (IPF) is a chronic disease characterized by progressive scarring of the lung. There is no cure and patients diagnosed with IPF have a median survival of 3-5 years after diagnosis. Novel therapeutic targets are needed, and several studies have implicated the serine protease inhibitor, plasminogen activator inhibitor-1 (PAI-1) in the promotion of pulmonary fibrosis. Studies by our lab and others have shown that PAI-1 is significantly upregulated in fibrotic lung tissue, and that PAI-1 expression correlates with severity of scarring. However, the mechanism through which PAI-1 promotes pulmonary fibrosis is still unknown. We recently used a proteomics screen to look for potential PAI-1 interactors in fibrotic lungs of mice and identified several candidate proteins, including G3BP1, a stress granule protein. G3BP1 drives the assembly of stress granule proteins and has also been implicated in the development of various cancers. Furthermore, PAI-1 has previously been shown to be sequestered in stress granules as cells transition between different functional states. We hypothesize that there is an interaction between PAI-1 and G3BP1 in cells that mediates their profibrotic phenotype. We will measure the protein expression of PAI-1 and G3BP1 in normal and IPF human lung tissue, and we will perform binding assays in order to determine if PAI-1 binds with G3BP1 in human lung tissue. Lastly, we will examine if there is colocalization of PAI-1 and G3BP1 in cells under stressful conditions via immunofluorescence. Determining if there is an interaction between these two proteins will allow us to gain a better understanding of the mechanisms of IPF.
