Project at a glance

The main interests of our lab are the molecular mechanisms underlying airway epithelial cell repair in the context of cystic fibrosis, an infectious and pro-inflammatory genetic lung disease.

Cells communicate between each other to coordinate their response to external stimuli. Gap junctions are transmembrane channels that directly connect the cytoplasm of cells in contact. Gap junctions interconnect airway epithelial cells that constitute the respiratory epithelium, a physical barrier at the interface between innate and adaptive immunity. This immunity, however, is jeopardized in cystic fibrosis (CF), a genetic disease caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Electrochemical signaling between CF epithelial cells is altered in this disease whereas gap junctions are critical for organ development and function. CFTR regulates the activity of gap junction channels and gap junctional intercellular communication (GJIC) contributes to the defense mechanisms of airway epithelial cells to infection. Recent reports point to a role of CFTR in the repair of the airway epithelium, suggesting that parts of the complex lung phenotype in CF may result from abnormal differentiation after injury. Possibly, defective electrochemical signaling could have an impact on epithelial cell fate in CF.

The first part of our research is to understand the molecular links between CFTR dysfunctions and abnormal GJIC on airway epithelial cell integrity. The second part of our research aims at identifying key transcriptional pathways in human lung repair and characterize those which are deregulated in CF. Better understanding of these aspects are required to optimize and develop therapeutic strategies to reduce severity of the CF airway disease, which causes irreversible lung damage to the patients.