Department of Infectious Diseases
Associate Professor
Expertise

Bacteriology | Disease Modeling | Immunology | Infectious Diseases | Microbiology

Biography

Research Interests

Role of reactive oxygen species in host-microbe interactions at the respiratory mucosa, neutrophil biology, Pseudomonas aeruginosa infection in cystic fibrosis ​

Educational Background

  • ​BSc (1998; Microbiology), Eötvös Loránd University, Budapest
  • PhD (2005; Medical Physiology), Semmelweis University, Budapest
  • Postdoctoral fellowship (2005-2011): Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland

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.

Selected Publications

Rada B , Jendrysik MA, Pang L, Hayes CP, Yoo DG, Park JJ, Moskowitz SM, Malech HL, Leto TL. Pyocyanin-enhanced neutrophil extracellular trap formation requires the NADPH oxidase. PLoS One. 2013;8(1):e54205.

Chen Z, Xu P, Salyards GW, Harvey SB, Rada B , Fu ZF, He B. Evaluating a parainfluenza virus 5-based vaccine in a host with pre-existing immunity against parainfluenza virus 5. PLoS One. 2012;7(11):e50144.

Rada B , Leto TL. Pyocyanin effects on respiratory epithelium: relevance in Pseudomonas aeruginosa airway infections. Trends Microbiol. 2013 Feb;21(2):73-81.

Boudreau HE, Casterline BW, Rada B , Korzeniowska A, Leto TL. Nox4 involvement in TGF-beta and SMAD3-driven induction of the epithelial-to-mesenchymal transition and migration of breast epithelial cells. Free Radic Biol Med. 2012 Oct 1;53(7):1489-99.

Waisberg M, Cerqueira GC, Yager SB, Francischetti IM, Lu J, Gera N, Srinivasan P, Miura K, Rada B , Lukszo J, Barbian KD, Leto TL, Porcella SF, Narum DL, El-Sayed N, Miller LH, Pierce SK. Plasmodium falciparum merozoite surface protein 1 blocks the proinflammatory protein S100P. Proc Natl Acad Sci U S A. 2012 Apr 3;109(14):5429-34.

Nemeth K, Wilson T, Rada B , Parmelee A, Mayer B, Buzas E, Falus A, Key S, Masszi T, Karpati S, Mezey E. Characterization and function of histamine receptors in human bone marrow stromal cells. Stem Cells. 2012 Feb;30(2):222-31.

Yu M, Lam J, Rada B , Leto TL, Levine SJ. Double-stranded RNA induces shedding of the 34-kDa soluble TNFR1 from human airway epithelial cells via TLR3-TRIF-RIP1-dependent signaling: roles for dual oxidase 2- and caspase-dependent pathways. J Immunol. 2011 Jan 15;186(2):1180-8.

Rada B , Gardina P, Myers TG, Leto TL. Reactive oxygen species mediate inflammatory cytokine release and EGFR-dependent mucin secretion in airway epithelial cells exposed to Pseudomonas pyocyanin. Mucosal Immunol. 2011Mar;4(2):158-71.

Rada B , Leto TL. Characterization of hydrogen peroxide production by Duox in bronchial epithelial cells exposed to Pseudomonas aeruginosa. FEBS Lett. 2010 Mar 5;584(5):917-22.

Rada B , Leto TL. Characterization of hydrogen peroxide production by Duox in bronchial epithelial cells exposed to Pseudomonas aeruginosa. FEBS Lett. 2010 Mar 5;584(5):917-22.

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