CF milestones at UI and beyond

Discovery that cystic fibrosis (CF) disrupts chloride transport across airway epithelium, and the defect is localized to the apical (air-side) surface of the cells (PNAS).

University of Iowa Cystic Fibrosis Research Center established.

Cystic fibrosis transmembrane conductance regulator (CFTR) gene discovered.

UI team finds expressing recombinant CFTR in CF cells corrects CF chloride defect (Nature).

UI team determines CFTR is a chloride channel (Science). 

UI researchers discover that CF airway cells fail to secrete bicarbonate ions (J. Clin. Invest.)

Beginning of National Institutes of Health funding for UI CF researchers; more than $80 million awarded to date. 

UI team develops classification system describing how different genetic mutations can “break” the CFTR protein (Cell). System still used today, has guided development of therapies to repair the breaks.

UI launches first human trials of gene therapy for CF (Cell).

UI provides Vertex Pharmaceuticals with cells expressing functional and mutated CFTR, enabling high-throughput screening of drugs to correct CF defect.

Pig model of CF developed by UI and University of Missouri teams (Science). 

Ferret model of CF developed at UI (J. Clin. Invest.).

Kalydeco approved by Food and Drug Administration to treat certain forms of CF; tested at UI.

UI determines airway surface liquid more acidic in CF lungs, suggesting new treatment possibilities (Nature).

UI team shows mucociliary transport defective in CF at birth (Science).

UI researchers discover a proton pump, ATP12A, secretes acid into airways of people and pigs with CF; experimentally disabling ATP12A in pigs with CF halts development of lung infection (Science).