CAREER: Propagation of Lung Fibrosis through Mechanotransduction

Virginia Commonwealth University, Richmond VA

Investigators

Abstract

The research objective of this Faculty Early Career Development (CAREER) Program award is to test the hypothesis that mechanical stretch of alveolar epithelial cells propagates lung fibrosis. Epithelial injury is a central event in the progression of fibrotic lung diseases like acute respiratory distress syndrome, pulmonary fibrosis, bronchopulmonary dysplasia, and ventilator induced lung injury. Mechanical strain is an often underappreciated contributor to lung epithelial injury. This project will test the hypothesis through three research goals utilizing a multi-scale approach toward mechanotransduction from lung tissue deformation to sub-cellular molecular signaling. These studies will improve fundamental scientific knowledge by explaining mechanisms that are responsible for aberrant repair and fibrosis in alveolar type II epithelial cells. In addition to providing a better understanding of fibrosis in the lung, the results of these experimental studies will provide a new understanding of the mechanotransduction of epithelial cells that may be applicable to the epithelium of several different organs and diseases. A learning platform with hands-on demonstrations of epithelial cell mechanobiology will be developed as an outreach tool to teach under-represented middle school students. As an extension of the middle school modules, this project will develop course materials for high school education in mechanobiology. Furthermore, this work will provide a basis for a new Undergraduate and Graduate Course offering in Biomedical Engineering, "Cell Mechanics and Mechanobiology". Additionally, research opportunities will be available for high school students through the Medical Sciences Internship Program and to undergraduates through the Honors Summer Undergraduate Research Program. The research and educational goals will impact many under-represented students at a variety of levels and have high impact on human fibrotic lung disease.