CCBIO-seminar – Thomas H. Barker
Velkommen til CCBIOs seminarserie for høstsemesteret i 2023. Foreleser er Thomas H. Barker, professor i Biomedical Engineering på the University of Virginia, Charlottesville, USA. Tittel: “Targeting the Matrix in a matrix-centric disease: The holy grail of Fibrosis therapeutics?” Åpent for alle i auditorium 4, BBB. Registrering er ikke nødvendig.
(Engelsk tekst videre siden seminarene er internasjonale og undervisningsspråket på seminarene er engelsk.)
Speaker: Thomas H. Barker, Professor of Biomedical Engineering, Cell Biology and Pulmonary and Critical Care Medicine, Schools of Engineering and Medicine, University of Virginia, Charlottesville, USA
Title: “Targeting the Matrix in a matrix-centric disease: The holy grail of Fibrosis therapeutics?”
Host: Donald Gullberg
Where: Auditorium 4, BB-building
When: December 14, 2023 at 14.30-15.30
No registration necessary.
Abstract: Idiopathic Pulmonary Fibrosis (IPF) and other lung interstitial diseases (ILDs) represent a diverse set of clinical scenarios that all culminate in the excessive deposition of extracellular matrix (ECM) in the lung, i.e. progressive fibrosis. Fibroblasts are the arbiters of the gross ECM remodeling that characterizes these diseases, and it is believed that targeting the emergence of fibroblasts and their signaling represents the most tractable approach for disease treatment. Indeed, most pipeline therapeutics are focused on mechanisms of alveolar epithelial cell EMT, fibroblast activation and myofibroblast differentiation (eg. TGF activation and WNT downstream signaling). These emerging approaches are significantly more advanced than the current standard of care yet remain somewhat myopic to the underlying ECM’s dominant impact on epithelial cell, endothelial cell, pericyte and fibroblast behaviors, which underpin both TGFb and WNT signaling. Despite fibrosis being best characterized by ECM deposition, no current or pipeline therapeutics target this foundational piece of the fibrosis puzzle. This is in large part due to the gross similarities in ECM composition between fibrotic and normal tissue. While the stoichiometries may differ, the molecular signatures are highly similar making targeting a fraught enterprise. Over the past decade or more my group has explored the emergence and impact of alternative conformations of the critical ECM protein fibronectin in tissue repair and remodeling. In this seminar, I will review our findings that demonstrate a modest and pathophysiologically relevant force-driven conformational change in fibronectin’s integrin binding domain can drive numerous disease phenotypes and yet can be leveraged to specifically target fibrosing tissues with the potential to reverse fibrotic remodeling.