Grant: Foundation Grant

Different precursor cells are activated to rapidly repair injured tissues. Examples for injury are skin trauma or burn wounds, infarct or chronic overload of the heart, lung epithelium damage, liver infection or alcohol abuse, and kidney damage because of high blood pressure. The activated cells are called myofibroblasts (MFs) because they secrete fibrous collagen matrix ("fibro") that is contracted ("myo") into mechanically stabilizing scar tissue. Although MFs are essential to restoring mechanical integrity of damaged tissue, they never truly regenerate organs and scar formation comes at the cost of reduced organ function. Worse, MF deregulation leads to excessive tissue and organ scarring - a condition called fibrosis. Fibrosis contributes to ~45% of deaths in industrialized nations by causing malfunction and failure of vital organs, such as heart, liver, kidney, lung, and vasculature. Fibrosis promotes tumor progression in the stroma reaction, leads to implant failure in foreign body responses, jeopardizes mesenchymal stem cell therapies by turning stem cells into scar cells and disfigures skin. MFs are key pharmaceutical targets but anti-MF therapies have not yet been translated to clinical treatments of fibrosis. Identifying the joint mechanical and biochemical regulators of MFs, which are incompletely understood, will be essential to promote healing with intervention therapies. Our unrivalled, state-of-the-art research will provide new insights into understanding disease progression, establish novel markers for wound healing therapies, enable the production of innovative technology for use in mechanobiology cell studies, and develop industry-standard drug screening devices. New drug targets, screening tools, biomarker and treatment strategies have tremendous commercial potential/value and will improve the quality of life of fibrosis patients in Canada and worldwide.