Please find below some information on our current projects (as of October 2014). The projects evolve constantly. Please do not hesitate to contact us for further information.
Pneumonia and Acute Lung Injury
Our major aim in this field is the development of new preventive and therapeutic options for pneumonia and acute lung injury (ALI) on the basis of an enhanced understanding of pathophysiology.
Recent and current projects examine pulmonary bacterial-host interaction, cellular and humoral mechanisms in innate immunity, as well as endothelial alterations and barrier dysfunction. Isolated pathogenic factors, bacterial mutants and genetically modified mice are employed, and the studies are conducted on different levels: in vitro, ex vivo (e.g. isolated perfused and ventilated mouse lung) and in vivo in models of pneumonia (including S. pneumoniae, L. pneumophila, Influenza virus, C. pneumoniae) and sepsis (S. pneumoniae, Pneumolysin, LPS, CASP) in our ´mouse-ICU´. Employment of primary human cell and tissue cultures as well as specimen of human pneumonia patients strengthens the methodological approach.
In a network project, we are following a systems medicine approach to improve our understanding of the development of ARDS in pneumonia in a comprehensive way.
Ventilator induced lung injury
In acute respiratory failure, mechanical ventilation (MV) is a life saving treatment without alternatives. One third of all patients in intensive care units worldwide are receiving MV. However, particularly in preinjured lungs even minimal MV-associated physical stress is translated into biological signals of inflammation, evoking ventilator-induced lung injury (VILI). VILI is characterized by liberation of cytokines, recruitment of leukocytes to the lung and increased lung permeability, consecutively resulting in lung edema, surfactant dysfunction, impaired lung compliance and deterioration of pulmonary gas exchange. Clinical studies revealed that minimization of MV-induced physical stress by reduction of tidal volumes to 6 ml/kg significantly improved outcome of mechanically ventilated patients with ARDS. However, even low tidal volume ventilation of healthy lungs causes lung injury, particularly in lungs preinjured due to e.g. pneumonia. As the necessity to guarantee sufficient gas exchange limits a further substantial reduction of tidal volumes, new adjuvant pharmacological therapies in addition to lung-protective ventilation are needed to prevent VILI. Thus, we aim to enhance the understanding of pathomechanisms underlying VILI in order to develop new therapeutic strategies to limit VILI.
Recent work by our group showed that infusion of the endogenous peptide Adrenomedullin or treatment with simvastatin attenuates VILI in mice (Thorax 2010; Crit Care 2010; PloS One 2012; Crit Care 2014).
Our specific interest in asthma research lies in the development of novel therapies and the improvement of experimental models of allergen-induced airway inflammation using different models of acute and chronic allergen-induced lung inflammation. For example, we recently found that vitamin D is essential for successful specific hyposensitization (J Immunol 2014) and that ligation of the Nucleotide Oligomerization Domain-1 reduces TH2-inflammation (Am J Resp Cell Mol Biol 2014). We further established the first mouse video-bronchoscope worldwide (Am J Resp Cell Mol Biol 2014) to enable for localized allergen challenge of mouse lungs and for repetitive analysis, which reduces the number of animals needed for asthma research. Our current research is focusing on specific tyrosine kinases as novel therapeutic targets in allergen-induced airway inflammation.
Inflammation associated pathogenesis of pulmonary arterial hypertension
The role of lung inflammation in the pathobiology of pulmonary arterial hypertension (PAH) represents a further field of interest. More precisely, together with collaborators we recently investigated specific aspects of inflammation in PAH associated with systemic sclerosis (Am J Resp Crit Care Med. 2014) and in hypoxia-induced PAH (Am J Resp Crit Care Med. 2013; J Clin Invest. 2012). Further, we described the development of pulmonary vascular hyperresponsiveness and remodelling in allergen-induced lung inflammation (Eur Resp J., 2006) and identified sphingosine kinase-1 as a central regulator in this process (J Allergy Clin Immunol., 2009).