"Biomechanical Signaling in Pulmonary Fibrosis" 

Daniel J. Tschumperlin, PhD
Associate Professor of Physiology & Biomedical Engineering
Mayo Clinic College of Medicine

The research of Daniel J. Tschumperlin, PhD, focuses on the respiratory system and how the structure, function and mechanics of the lung are regulated in health and disease.

Pulmonary fibrosis is a devastative disease that affects ~40,000 patients in the US, with a median survival of 3-5 years and no proven therapies.  Fibrosis stiffens the lungs as it reshapes the extracellular matrix, leading them to hypothesize that mechanical feedback from the stiffened matrix may be critically important to ongoing fibroblast activation and the progressive nature of the disease.  They have developed methods to mechanically characterize lung tissue mechanical properties using atomic force microscopy, and to study isolated lung cell behaviors on matrices spanning the pathological range of elastic moduli observed in the lung.  These studies indicate that normal lung fibroblasts transition from a quiescent state on physiologically soft matrices to a proliferative, contractile and matrix synthetic state on pathologically stiff matrices, implicating the matrix mechanical environment as a key factor in the persistently activated state of these cells in vivo.  Their recent work has focused on identifying biochemical pathways by which the mechanical environment influences fibroblast biology.  Microarray analysis of matrix-stiffness regulated genes in human lung fibroblasts identified highly significant overrepresentation of transcriptional targets of YAP (yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif). In this presentation he will detail ongoing studies documenting a central role for YAP and TAZ as mechano-activated regulators of fibroblast function and pulmonary fibrosis.

Thomas Barker, PhD - faculty host