Project Details
Projekt
Reversing mechanical stress induced remodelling in idiopathic pulmonary fibrosis
Subject Area
Pneumology, Thoracic Surgery
Cardiac and Vascular Surgery
Cardiac and Vascular Surgery
Term
from 2016 to 2021
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 286251789
Idiopathic pulmonary fibrosis (IPF) is a fatal disease with a mean survival time of 3 years. New treatment options are urgently warranted. IPF is characterized by a vast remodeling of the alveolar compartment which results in a loss of alveoli and replacement by non-functional replacement tissue and scarring. Mechanical stress is fundamentally linked to the pathogenesis of IPF and thought to drive the disease by TGF-beta activation. The exact mechanisms induced by mechanical stress however are only rudimentarily understood. The intended project aims to investigate mechanisms induced by increased mechanical load in IPF applying molecular biology and new imaging techniques. The focus lies on TGF-beta signaling induced by mechanical stress and the role of avbeta6 integrin and CXCR4 in this context. In mice and humans with pulmonary fibrosis CXCR4 and avbeta6 integrin will be imaged by positron emission tomography (PET) in vivo and correlated with cell and molecular biology findings. In addition, we will use the organ care system (OCS) to image mechanical stress in explanted IPF lungs by newly developed algorithms based on computer tomography (CT) scanning. On the basis of our achievements we will develop new therapeutical strategies which utilize the CXCR4, avbeta6 and PDGF radio nuclear tracers bound to alpha emitters. Treatment effects will be tested in a humanized mice model and in explanted lungs using the OCS. Moreover extra corporal membrane oxygenation (ECMO) and the organ care system will be evaluated as temporal unloading of mechanical stress to allow reverse remodelling.
DFG Programme
Clinical Research Units
