Objective Chronic obstructive pulmonary disease (COPD), a global health problem, will be the third leading cause of death by 2020. No effective therapy exists for COPD, which is characterized by a progressive loss of lung tissue, in particular functional alveolar epithelium, due to the inability of the lung to regenerate. Thus, regeneration of functional lung tissue would be a tremendous step forward, which has not been demonstrated as of yet.The alveolar epithelium is essential for normal lung function and composed of alveolar type I (ATI) and type II (ATII) cells. ATII cells serve as progenitors for alveolar epithelial restoration via differentiation into ATI cells. Induction of lung regeneration requires a tight interplay between initiating and differentiating factors acting on the alveolar epithelium.The overall aim of this proposal is to explore the regenerative potential of the adult human lung, driven by the alveolar epithelium. We will utilize an ex vivo lung regeneration model, characterize ATI/II cells in diseased lungs, and explore novel initiating and differentiating factors in vivo and ex vivo.WNT/²-catenin signaling is a promising initiating factor for lung regeneration. We have recently demonstrated a crucial role of WNT/²-catenin signaling in alveolar epithelial cell repair in lung disease. Further, embryos lacking WNT2/2b expression exhibited complete lung agenesis, demonstrating the requirement of WNT/²-catenin signaling in lung generation. We will explore WNT/²-catenin signaling in ATI/II cells, and the regenerative potential thereof. We will analyze the ATI/II cell phenotype in mouse and human COPD specimen, to identify novel differentiation factors facilitating lung regeneration.We will consolidate our findings by testing the therapeutic applicability of initiating and differentiating factors in COPD in our ex vivo human lung regeneration model. This will lead to reliable and validated results that will be successfully translated into the clinic. Fields of science medical and health sciencesclinical medicineembryology Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) ERC-SG-LS7 - Applied life sciences, biotechnology and bioengineering: agricultural, animal, fishery, forestry/food sciences; biotechnology, chemical biology, genetic engineering, synthetic biology, industrial biosciences; environmental biotechnology. Call for proposal ERC-2010-StG_20091118 See other projects for this call Funding Scheme ERC-SG - ERC Starting Grant Host institution HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT GMBH EU contribution € 1 291 670,00 Address INGOLSTADTER LANDSTRASSE 1 85764 Neuherberg Germany See on map Region Bayern Oberbayern München, Landkreis Activity type Research Organisations Administrative Contact Juergen Ertel (Dr.) Principal investigator Melanie Königshoff (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data Beneficiaries (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT GMBH Germany EU contribution € 1 291 670,00 Address INGOLSTADTER LANDSTRASSE 1 85764 Neuherberg See on map Region Bayern Oberbayern München, Landkreis Activity type Research Organisations Administrative Contact Juergen Ertel (Dr.) Principal investigator Melanie Königshoff (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
