Grant: Project Grant

Cystic fibrosis (CF) is a genetic disease that can cause severe, life-shortening lung complications. In recent years, effective treatments that benefit many people with CF have been developed, but there are some people with rare CF gene mutations who cannot benefit from such medications. The CF community anticipates the development of new treatments that directly target the defective CF gene (e.g. gene therapy) and could treat all people with CF. Researchers developing these next-generation CF treatments need to know which cells to fix and where they exist in lungs. Unfortunately, we do not fully understand which lung cells are responsible for causing CF lung disease. We propose to study human airway (the air passages in lungs) tissue obtained from lung transplant surgeries as well as animal lungs. In particular, we will study ionocytes, a recently discovered cell type, and club cells to determine in detail their role in causing CF lung disease. We are interested in these cells because studies have suggested that ionocytes and club cells are the cause of key problems in CF lung disease. We will use state-of-the-art techniques to measure the function of cells in the lungs from human donors and CF animal models and describe how each cell works in health and disease. Our strategy of using human tissue is unique and sets our research apart from other studies because it is the best way to study CF. Our results will describe which cells need to be fixed for curing CF, and will lead to improved treatments for CF lung disease. Based on our work thus far, we believe that ionocytes and club cells have different roles; fixing one but not both types of cells may not cure CF.