15. Identifying Nuclear Membrane Proteins that Facilitate Chromosomal Mechanotransduction

Idiopathic Pulmonary Fibrosis (IPF) is an end-stage lung disease that is mediated by force interactions within the lung epithelium. The current standard of care aims to reduce the symptoms of the disease through non-curative drug treatments or by lung transplantation. Our team aims to determine an additional upstream target that would reduce the progression of fibrosis. We hypothesize that LRP-130, CAPZ-α, and MATR3 play a role in force mechanotransduction and ultimately IPF. To determine the proteins involved in the mechanosensitive signaling pathway, a magnetic precipitation technique is used to pull down the proteins involved. These proteins are then analyzed through proteomics techniques such as western blotting and immunofluorescence. A knockdown study was performed to determine the individual role the proteins play in YAP/TAZ nuclear translocation. LRP-130, CAPZ-α, and MATR3 have been established as potential proteins in the pathway and have been identified in samples subject to force. The localization of these proteins has been linked to the nuclear membrane. Additional knockdown studies will be performed to determine the extent to the protein’s effect on YAP/TAZ nuclear translocation. Overall, we have observed that these proteins play a role in regulating the cellular response to force mechanotransduction. This work is significant to the future of IPF treatments as these proteins serve as potential targets for curative therapies.