PROJECTS

Please find below some information on our current projects (as of June 2018). 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 are employed, and the studies are conducted on different levels. 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.

Furthermore the long-term aim of the Project Phage4Cure is to establish bacteriophages as drugs in the fight against bacterial infections and as such gain legal authorisation as medicinal products in a variety of dosage forms for different indications.

Vaccination

Immunization is the most important prophylactic strategy used worldwide to prevent invasive bacterial diseases. However, existing polysaccharide vaccines are subject to several limitations. An innovative chemical method recently established by our collaborator now enables the rapid synthesis of structurally defined oligosaccharide antigens with optimized immunogenic properties based on the binding specificities and structural features of protective antibodies (Seeberger PH et al. Curr Opin Chem Biol 2009). Together with our collaborators, we are currently evaluating highly promising vaccine candidates for their immunostimulatory and -protective capacity in preclinical in vitro and in vivo studies

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.  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.
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).  Another approach is to explore the mechanisms by which the circadian rhythm  influences innate immune response to MV.

Asthma bronchiale

We established the first mouse video-bronchoscope worldwide (Am J Resp Cell Mol Biol 2014) to enable for localized allergen challenge and repetitive analysis, and to reduce animal numbers. Our specific interest lies in the development of novel therapies by investigating different models of acute and chronic airway inflammation. Recently, we found that inhibition of spleen tyrosine kinase improved the main hallmarks of asthma, namely airway (hyper-) responsiveness, allergic airway inflammation and airway remodeling (Allergy 2017). Another goal is to optimize the long-term effects of allergen-specific immunotherapy e.g. by vitamin D supplementation (J Immunol 2014).

Pulmonary hypertension

Together with our collaborators, we recently uncovered central mechanisms of hypoxic pulmonary vasoconstriction (Eur Respir J 2017; Proc Natl Acad Sci U S A 2015; J Clin Invest 2012) and established the role of functional autoantibodies in pulmonary arterial hypertension associated with systemic sclerosis (Am J Resp Crit Care Med 2014). Further, we described the development of pulmonary vascular hyperresponsiveness and remodeling due to pulmonary Th2 inflammation (FASEB J 2011; J Allergy Clin Immunol 2009; Eur Resp J 2006). Current research is also focusing on spleen tyrosine kinase as a novel therapeutic target in PH (Am J Respir Crit Care Med 2017;195:A2272).