Grant: Project Grant

Idiopathic pulmonary fibrosis (IPF) is a type of lung fibrosis where the lungs slowly get scarred, making it harder to breathe and eventually leading to death. Each year, 14,000 Canadians get IPF, and for 40% of them, their quality of life is seriously affected, with an average survival time of 3 to 5 years. Right now, IPF can't be cured therapeutically and lung transplant is the only option for those suffering from IPF. We want to focus on finding better treatments for IPF and lung fibrosis in Canada and around the world. Our idea is to create a new treatment for IPF by targeting certain proteins that control how a key molecule called transforming growth factor beta (TGFB) causes fibrosis. TGFB plays a big role in scarring but has been hard to target therapeutically as TGFB plays a number of roles throughout the body. We found that a protein called Beta Ig H3 (BIGH3), which is released after TGF-B signaling, may be important for the fibrosis pathogenesis that TGF-B drives and that by targeting BIGH3, we may be able to ameliorate lung fibrosis without impacting the role of TGFB in other processes. Moreover, BIGH3 signals through integrins, which, like TGFB are broadly expressed on many cells. By targeting BIGH3, we may have an opportunity to limit TGFB and integrin signaling in a context specific manner. Here, we use cell culture and animal models to understand how BIGH3 can be targeted to manage lung fibrosis.