Mechanobiology of Pulmonary Fibrosis

This project aims to precisely define the spatial and temporal changes in tissue stiffness that accompany fibrosis and identify the signaling mechanisms that regulate mechanical activation of fibroblasts. Model systems are being used as well as human disease-derived cells and tissues.

Fibrosis is a pathobiological process common to many tissues and diseases that results in tissue remodeling and loss of function, often necessitating organ replacement or leading to end-stage disease. Fibrosis occurs predominantly in soft tissues, such as lung, liver, kidney, heart and skin, through fibroblast activation. Activated fibroblasts are contractile, proliferative and apoptosis-resistant, and are responsible for the excess deposition of extracellular matrix. Fibrosis dramatically stiffens soft tissues; this matrix stiffening by itself promotes fibroblast proliferation, matrix synthesis and contraction, establishing a feedback loop that amplifies this pathological process.

The long-term goal of this research is to elucidate molecular mechanisms of stiffness-dependent fibroblast activation, thus identifying novel regulators of fibrogenesis suitable for therapeutic targeting.