Balazs Rada

Activities

Research in my laboratory investigates reactive oxygen species-based host-microbe interactions in the respiratory mucosa. Reactive oxygen biology in the airways is of extraordinary relevance because of the continuous exposure to atmospheric oxygen tensions, levels higher than in most human tissues. Reactive oxygen species are crucial for the innate immune function of the airways but their uncontrolled production can cause tissue damage contributing to pathologies of diseases like cystic fibrosis, chronic obstructive pulmonary disease and pneumonia. Our current research efforts focus on the following projects:

Cystic fibrosis (CF) is an inherited disorder affecting several organs in the body but the main complications arise from chronic bacterial infections in the airways. The pathogenesis of CF lung disease is not entirely understood and current treatment options only retard the infection. CF airways are characterized by bacterial biofilm cultures, mucus overproduction and excessive infiltration of inflammatory white blood cells, neutrophil granulocytes. Upon activation neutrophils release web-like structures, neutrophil extracellular traps (NET) to entrap bacteria. NETs have been detected in CF airways but their role in disease pathogenesis remains unclear. NET release is mediated by reactive oxygen species produced by the phagocytic NADPH oxidase. To better understand the complex inflammatory environment in CF we study mechanisms of NET formation and superoxide production in the presence of Pseudomonas aeruginosa, the main bacterial pathogen in CF airways.
Pseudomonas aeruginosa uses several virulence factors to establish infections in the airways of CF, chronic obstructive pulmonary disease (COPD) and bacterial pneumonia patients. One of its most important virulence factors is a redox-active blue pigment, pyocyanin. Pyocyanin is a fascinating bacterial toxin with a wide range of toxic effects on the host. Previously we have shown that pyocyanin-initiated oxidative stress in bronchial epithelial cells results in several inflammatory changes (proinflammatory cytokine release, mucin production, activation of EGFR signaling), all of which are characteristic features of CF lung disease. Our work continues to characterize the details of pyocyanin’s action in epithelial cells and neutrophil granulocytes to understand its role in disease progression in CF and COPD.