Speaker Dr Eleanor Feneck, Research Associate, Logan Group, Randall Centre for Cell and Molecular Biophysics

Title The role of fascial-derived fibroblasts and the secreted extracellular matrix in muscle disease pathology

Host Malcolm Logan

 

Abstract Our research investigates the role of fascial-derived fibroblasts (FDFs) in muscle development and disease. We show these fibroblasts co-ordinate the organisation of muscle fibres into individual muscle bundles during embryogenesis and that when dysfunctional in disease, disrupt the events that form muscle bundles. We investigate the role of FDFs in the human congenital connective tissue disease, Radial Dysplasia (RD). We show RD FDFs have a functional deficit causing them to secrete a pathological extracellular matrix that abnormally arranges muscle cells, which can explain the muscle defects present in patients at birth. Using proteomics and single cell sequencing we have identified mis-expressed extracellular matrix proteins that we predict contribute to disease progression. We show several matrix constituents are mis-regulated in the FDFs of RD patients and link these modifications to an increase in tissue stiffness and ultrastructural changes in collagen fibril architecture. Investigating treatment targets, we show we can recover FDF cell organisation, behaviour and extracellular matrix composition by targeting a signalling pathway. Our research aims to improve future diagnostic tools and treatment strategies for RD, with the aim to reduce disease progression and reoccurrence post-surgery.