Research

A major goal of the Gentzsch lab’s studies is to uncover potential targets for therapy of chronic lung diseases, including cystic fibrosis (CF). Dr. Gentzsch is a well-recognized expert in the cell biology of ion channels. Specifically, the lab focuses work on pharmacological modulation of airway epithelial ion channels such as CFTR (which is mutated in CF), ENaC (Epithelial sodium channel), and CaCC (Calcium-Activated Chloride Channel) in physiologically relevant model systems to develop pre-clinical models for CFTR research and drug discovery in CF.

To this end, the lab’s research is geared toward developing innovative techniques to evaluate modulation of ion channel function by small-molecule compounds in primary human bronchial and nasal epithelial cultures. This is done utilizing electrophysiological measurements in Ussing chambers (to measure electrical current across cell monolayers or epithelial tissues) as well as lipid bilayers (to look at single channels). To supplement these approaches, Western blots are used to follow protein production and maturation, immunofluorescence to visualize the protein inside cells and tissues,CF mouse models and intestinal, nasal, and bronchial organoids are also employed.

Our research is now investigating how environmental factors such as disease status, bacterial and viral infection, and inflammation affect ion channel function and protein interactions in airway epithelia. Furthermore, we are developing novel precision medicine models for other airway disease, where ion channel function is dysregulated (e.g., COPD/chronic bronchitis, asthma, hypoxia, chronic rhinosinusitis) . In addition, using our ion channel expertise, we are currently assessing the SARS-CoV-2 envelope viroporin as drug target to advance novel treatments for COVID-19 and other future coronavirus disease outbreaks.