Research

Mission

             The overall mission of the laboratory’s biomedical research program is to expand our knowledge of host-pathogen interactions in health and disease.

Our primary interest focuses on mechanisms used by the innate immune system to prevent or eliminate airway infections caused by viral and bacterial pathogens.

Our secondary interest studies how innate immunity promotes pathology in respiratory diseases.

The third focal point of our team’s research is to explore whether the innate immune system could be therapeutically manipulated to enhance microbial clearance and to attenuate inflammation-related tissue damage in respiratory infections.

Projects

Cystic fibrosis airway inflammation

Cystic fibrosis (CF) is a genetic disease affecting an estimated 160,000 individuals worldwide. Of these, ~105,000 CF patients are diagnosed and ~20,000 patients receive the most recent, ivacaftor/tezacaftor/elexacaftor triple combination therapy. CF is a multi-systemic, life-threatening, autosomal, recessive disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Progressive and obstructive lung disease due to chronic airway infections coupled with impaired host immunity, is the leading cause of morbidity and mortality in CF.

The clinically most important immune cell type driving CF lung inflammation, especially in adults, is the neutrophil. Neutrophils are innate immune cells that are professional phagocytes produced to kill microorganisms. In CF, however, neutrophils fail to eliminate a select group of respiratory pathogens and induce lung damage instead. Understanding the mechanisms of impaired antimicrobial clearance and lung tissue damage by neutrophils are clinically highly relevant to CF. People with CF suffer from polymicrobial lung infections throughout their lifetime.

      Pseudomonas aeruginosa has been the most prevalent pathogen in CF airways up to ten years ago. P. aeruginosa is an opportunistic pathogen that undergoes a microevolution in the lungs of people with CF over the years. P. aeruginosa establishes biofilms in CF that are hard to eradicate by the immune system or by medical interventions. We have studied the interaction of P. aeruginosa with neutrophils and described that CF clinical isolates of the bacterium induce the formation of neutrophil extracellular traps. NETs are, however, inefficient in killing the bacterium and likely further promoted bacterial biofilm formation.

Cystic fibrosis autoimmunity

Oxidative antimicrobial mechanisms of the airways

Enhancing airway oxidant production to attenuate respiratory infections