Research Summary

"Research in my laboratory focuses on two areas: (1) cystic fibrosis lung disease and (2) congenital inner ear defects leading to deafness and balance disorder.

(1) Patients with cystic fibrosis (CF) suffer from severe airway infections that destroy the lungs. However, the pathogenesis of the airway immune defect has not been delineated, and the current antibiotics-based treatment of CF only slows down the progression of the disease. We have recently demonstrated that healthy airways possess a reactive oxygen species (ROS)-producing system that kills bacteria with great efficiency. In contrast, CF airway cells lack one component of the ROS-producing system, which leads to drastically reduced antibacterial activity and may explain (in part) why CF patients suffer from recurrent respiratory tract infections. We are studying the possibility of restoring the ROS-mediated host defense system in CF airways, and of thereby improving the lives of CF patients. In parallel with this therapy-focused project, we are pursuing a more detailed understanding of the biology and biochemistry of the ROS-dependent antibacterial mechanism of airways.

(2) Hearing and balance disorders are very frequent among the population, and developing new knowledge that would help in tackling these diseases will have a broad impact on quality of life. The human genome encodes 7 ROS-producing enzymes, one of which (NADPH oxidase 3) is expressed in the inner ear as part of a multisubunit enzyme complex. This particular oxidase complex is required for the formation of small calcium carbonate crystals, called otoconia (a.k.a. otolith), in the vestibular system; mutant mouse strains lacking an active inner ear NADPH oxidase do not generate otoconia, cannot sense gravity, and have severe balance disorders. We are currently investigating the mechanism by which the inner ear NADPH oxidase regulates the genesis of otoconia, a project that is also expected to lead to an understanding of the biological functions of other NADPH oxidases (e.g. Nox1, Nox4, and Nox5). As an extension of the inner ear NADPH oxidase project, we are searching for novel proteins required for the development and survival of sensory hair cells."