Research Area Leaders
T.Acker, T. Chakraborty, V. Grau, F. Grimminger, A. Günther, H. Hackstein, S. Herold, M. Kracht, W. Kummer, J. Lohmeyer, P. Markart, K. Mayer, R.E. Morty, J. Pfeilschifter, S. Offermanns, K.T. Preissner, S. Santoso, L. Schäfer, L. Schmitz, W. Seeger
Survival in severe respiratory infection critically depends on prevention and/or repair of endothelial and epithelial barrier failure. We have identified key regulators of endothelial/epithelial barrier function, including novel pathogen/host mediators and signalling pathways directing barrier integrity. We will extend these studies to clarify mechanisms that underlie barrier failure and repair in pneumonia, ARDS and sepsis; and will exploit these pathways for novel treatment strategies. Studies will be performed in cell culture, mouse models of acute respiratory failure (bacterial/viral pneumonia; endotoxin-, acid-, and ventilator-induced lung injury) and lavage/blood samples from patient cohorts.
- We will dissect the role of specific sensor systems for foreign and endogenous “danger” signals (TLR, NLR, RLH) in lung injury and repair including the downstream signalling pathways.
- We aim to promote host defence capacity while maintaining barrier integrity, and will explore molecular pathways involved in leukocyte trafficking, neutrophil extracellular trap formation, endothelial Gq/11-mediated signalling, the role of prolyl hydroxylases in inflammation-hypoxia crosstalk, and epithelial overexpression of CCL-2, IL-22 and GM-CSF for therapeutic purposes.
- We will also evaluate resolvins, JNK-dependent pathways, anti-apoptotic strategies (e.g. anti- TRAIL and downstream signalling), inhaled peptides (Bβ15-42, intermedin), ion channel (ENaC) and ion pump (Na/K-ATPase) manipulation for resolution of inflammation and non-scarring tissue regeneration. The stimulation of lung-resident stem/progenitor cells and exogenous mesenchymal stem cells will also be evaluated.
- In clinical studies we will identify inflammatory versus regenerative signatures in lavage samples from pneumonia/ARDS lungs and evaluate the therapeutic impact of precursor lipids of resolvins, Bβ15-42 and mesenchymal stem cells.