The alveolo-capillary wall of the human lung is still an enigmatic area of our body. This filigree structure forms a complex 3-dimensional barrier exposed to over 10.000 liters of inhaled air per day. How does it maintain its function despite confrontation with pollutants and pathogens? We are working on the basic characterization of structures building this wall and their affection in inflammation and infection (BMBF network PROGRESS). Furthermore, we started to characterize the influence of physical factors such as fluid shear stress on the behavior of the barrier.
As we are searching for therapeutic interventions to stabilize this barrier, we identified an endogenous human peptide called adrenomedullin for the stabilization of lung barrier function in acute lung failure (European Medicines Agency, Orphan Medical Product Designation EMEA/OD/139/09). Two therapeutic interventions based on this concept are now under clinical development.
We continue with the investigation of lung-pathogen interaction by using two of the most common human lung pathogens, influenza A virus (IAV) and Streptococcus pneumoniae. Currently, the investigation of cell-specific IFN responses in the human lung to IAV and the role of the pneumococcal toxin pneumolysin for barrier malfunction are in focus. In particular, we are interested in the role of mitochondria in these processes (DFG SFB-TR84).
Most emerging human infectious diseases are zoonotic infections of the lung (e.g. new IAV strains, SARS-, MERS-coronavirus). We therefore started to standardize and validate our human lung infection model as a new tool for risk assessment by public health authorities (BMBF-network RAPID “Risk assessment in pre-pandemic respiratory infectious diseases”).
Since we believe that continuous improvement of human tissue preparation, culture, manipulation and cryopreservation techniques are key factors for the development of more human relevant models (not only for the lung) and to speed up translation into the clinical practice, the group works together with several interdisciplinary groups to expand appropriate experimental possibilities. Of note, the consistent use of human material could not only improve the human relevance of the data obtained, it will also considerably contribute to the reduction of animal use in biomedical sciences in the future.
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