Project Area A - Inflammatory Lung Diseases

Bronchial Asthma and COPD

Bronchial Asthma and COPD are causing a significant morbidity and high socio-economical costs. During the past years substantial progress has been made in understanding the pathogenesis of Asthma and COPD, which is directly related to the scientific research focus of the UGMLC faculty. Early intervention in asthma- und COPD-pathogenesis aiming at modifying the immunological programming is one of the main goals in this regard.To achieve this goal, the interactive networks on the levels of signal transduction (microRNAs, Wnt und Notch) and cell type (subtypes of B-/T -lymphocytes, macrophages, epithelial-, vascular muscle-, and stem cells) have to be analyzed. The role of microorganisms, at least as an amplification factor, for inflammatory processes shall be elucidated. Furthermore, the new findings of the UGMLC regarding mutual interaction of restructuring processes in the airways, the alveolar space, and the neuronal and vascular system shall be intensified. In this context, different types of asthma (eosinophilic, steroid-sensitive etc.) and COPD phenotypes (frequent or no-exacerbations) come into focus, which shall be differentiated with non-invasive procedures like the analysis of breath condensate and reproduced in animal models within the UGMLC. This could lead to important therapeutic progress in terms of personalized medicine. Finally, COPD is seen as a systemic disease which leads to an inflammatory spill-over into other organ systems.  Based on this knowledge we will further develop already identified as well as new therapeutic approaches and make these available to patients. The research program of the second funding period directly continues these important developments with focus on asthma and COPD phenotypes,  shared and differential (sub-cellular) networks of COPD and asthma, disease progression and remodeling, COPD as a systemic disease as well as new therapeutic approaches. Thus, this work program is distinguished from other consortia in the region, like the SFB TR22. The SFB TR22 focuses on the initiation of the allergic immune response, the pre- and postnatal immune programming, including complex gene-environment-interaction as well as allergic phenotypes.

Faculty members involved: Bauer, S., Bellusci, Braun, Chakraborty, Dammann, Domann, Fink, Garn, Gessler, Grau, Grimminger, Günther, Henke, Hossain, Huber, Koczulla, Kracht, Kummer, Nassenstein, Nockher, Pfefferle, Renz, Schermuly, Schmeck, Schmitz, Schnare, Seifart, Sittka, Steinhoff, Vogelmeier, Voswinckel, Weihe, Weißmann, Wilhelm, Wygrecka, Zemlin

 

Specific Projects

  1. Perpetuation of the disease process in asthma and COPD – role of the cell biological network
  2. Neuronal dysfunction in asthma and COPD
  3. Shared an differential signaling pathways in the pathogenesis of asthma and COPD
  4. Remodeling and fibrosis/regeneration in asthma and COPD
  5. Chronic inflammatory lung diseases as systemic diseases
  6. Novel therapeutic strategies in asthma and COPD

 

Pneumonia

The main research goal in this funding period, in addition to the further mechanistic elucidation of the pathogen-host interaction in the pneumonic inflammatory process, is the preclinical/clinical evaluation of identified mediators/target structures for therapeutic intervention strategies. Investigations will be carried out in murine and human organ cell cultures and lung models, in vivo pneumonia models of bacterial/viral pathogens as well as in clinical samples (blood, sputum, BALF) of patient cohorts. Potential targets and intervention strategies to be evaluated are:

1) the cell specific function of sensors for pathogen-host-coded danger signals (TLR, NLR, RLH) including downstream signal transduction

2) the molecular pathways of pulmonary leukocyte recruiting

3) resolvins and anti-apoptosis strategies to limit tissue damage

4) growth factors (e.g. GM-CSF) for lung resident stem-/progenitor cells and cell therapeutic approaches (e.g. intratracheally applied mesenchymal stem cells) to stimulate repair mechanisms and

5) small regulatory bacterial RNA-molecules to control pathogen growth.

In the long run chronologically and spatially optimized applications  of new targeted therapeutics for elimination of pathogens , attenuation  of pulmonary tissue damage and strengthening/acceleration of repair processes in the gas exchange compartment shall be developed, tested preclinically and be transferred  into clinical studies .

Faculty members involved: Al-Fakhri, Bauer, S., Bellusci, Braun, Chakraborty, Domann, Garn, Gessler, Grau, Grimminger, Günther, Hackstein, Hain, Hecker, Herold, Hossain, Kracht, Krasteva, Kummer, Lohmeyer, Markart, Matrosovich, Mayer, Pleschka, Preissner, Renz, Santoso, Schermuly, Schmeck, Schmitz, Schnare, Sittka, Vogelmeier, Voswinckel, Wygrecka

 

Specific Projects

  1. Microbial metagenome of the respiratory tract and pulmonary sensors for pathogens and inflammatory processes
  2. Pulmonary immune response in pneumonia: Mechanisms of the initiation and termination of inflammation/, pathogen elimination and tissue damage/repair in the alveolar space
  3. Intervention strategies

 

ARDS and Pneumogenic Sepsis

In ARDS and pneumogenic sepsis inflammatory processes and invading pathogens lead to dysfunction of the structural integrity and the essential gas exchange function of the lung, as well as to a cross-barrier spreading of infection and a dysfunctional systemic inflammatory response. Experimental and clinical studies aim at detecting cellular mechanisms and molecular signatures of ARDS and pneumogenic sepsis which lead to a loss of integrity and organ function and identifying them as targets for translation. Molecular, organ specific mechanisms of inflammatory reactions, which lead to a loss of compartmentalisation , disturbance of epithelial and endothelial barrier function and edema formation shall be characterized. Alveolar barrier protection, repair and regeneration via cell therapeutic strategies and use of new molecular (aerosolized) intervention techniques are of substantial significance.

Faculty members involved: Bauer, S., Günther, Hackstein, Hecker, Herold, Kracht, Kummer, Lohmeyer, Markart, Mayer, Morty, Preissner, Pullamsetti, Renz, Schermuly, Schmeck, Seeger, Vadasz, Vogelmeier, Weigand, Weißmann, Wilhelm

Specific Projects

  1. Molecular and genetic signatures of pneumogenic sepsis
  2. Contribution of the pulmonary inflammatory response to the pathogenesis of alveolar edema
  3. Interventional strategies restoring the alveolar barrier function