Lung Biology and Cystic Fibrosis Research Center

This timeline highlights a few of the many discoveries from the Cystic Fibrosis Research Center. 
For information about additional discoveries, see web pages of individual investigators.

1985 1990 1995 2000 2005 2010 2015
Widdicombe JH, Welsh MJ and Finkbeiner WE. Cystic Fibrosis Decreases the Apical Membrane Chloride Permeability of Monolayers Cultured from Cells of Tracheal Epithelium
Cystic fibrosis decreases the apical membrane chloride permeability of monolayers cultured from cells of tracheal epithelium
Sunday, September 1, 1985
One of first uses of cultured epithelia to explore CF
Localizes CF defect to a loss of chloride permeability in apical membrane of airway epithelia
Focuses attention on a chloride transport
University of Iowa establishes CF Research Center
Cystic Fibrosis Foundation RDP Established
Friday, January 1, 1988
University of Iowa establishes CF Research Center
Cystic fibrosis. Righting the wrong protein.
Expressing CFTR corrects the CF defect
Thursday, September 27, 1990
Expressing recombinant CFTR in CF cells corrects the CF chloride defect
Demonstrates causal relationship between mutations in CFTR gene and physiological hallmark of CF
Fuorescence microscopic assay suggests strategy for screening potential therapeutics
Demonstration that CFTR is a chloride channel
CFTR is a chloride channel
Friday, July 12, 1991
Discovery that CFTR is an chloride channel
Links genetic defect and physiological defect
Enables studies of CFTR function
Provides strategy for high throughput screens to develop drugs targeting CFTR
Discovery of complex regulation
ATP and phosphorylation regulate CFTR channels
Friday, September 6, 1991
Discovery of complex regulation of CFTR channels
Regulation by ATP at nucleotide-binding domains and by phosphorylation of R domain
Sets stage to modify CFTR regulation pharmacologically
Processing of mutant cystic fibrosis transmembrane conductance regulator is temperature-sensitive
Low Temperature Rescues CFTR-ΔF508
Thursday, August 27, 1992
Reducing incubation temperature partially rescues CFTR-ΔF508 processing and function
Ignites efforts to develop pharmaceuticals to correct mutant CFTR
cAMP stimulates bicarbonate secretion
CF airways lack bicarbonate secretion
Wednesday, April 1, 1992
Discovery that CF airways fail to secrete bicarbonate
Sets stage for exploring role of airway surface liquid pH in pathogenesis
Classification scheme describes how CFTR mutations disrupt function
Classification scheme for CFTR mutations
Friday, July 2, 1993
Classification scheme describes how CFTR mutations disrupt function
Facilitates understanding of genotype-phenotype relationships
Provides roadmap to develop mutation-specific treatments
First report of gene transfer to people with CF
Gene Transfer to People with CF
Friday, October 22, 1993
First report of gene transfer to people with CF
Suggests gene therapy is feasible. But, gene transfer is inefficient
Initiates attempts to identify barriers to gene transfer
Cellular and molecular barriers to gene transfer by a cationic lipid
Identification of barriers to gene transfer
Friday, August 11, 1995
Identified individual barriers to efficient gene transfer
Guides efforts to circumvent inefficiencies and improve gene transfer
Comparison of DNA-lipid complexes and DNA alone for gene transfer to cystic fibrosis airway epithelia in vivo
Identification of Barriers to Gene Transfer
Monday, September 15, 1997
First report of gene transfer to people with CF using a non-viral vector
Establishes feasibility, but also reveals inefficiencies
Cells to Vertex Enables Drug Screening
Thursday, January 1, 1998
Gift of 3T3 and FRT cells expressing wild-type CFTR and CFTR-ΔF508 to Vertex
Enables high throughput screens for drugs to correct CF defects
Biofilms in Cystic Fibrosis Lungs
Biofilms in Cystic Fibrosis Lungs
Thursday, October 12, 2000
Discovery that bacteria in CF lungs live in biofilms
Explains why CF infections are so resistant to treatment
Suggests new therapeutic strategies
CFTR is an adenylate kinase
Friday, December 26, 2003
CFTR is an adenylate kinase
Identifies two distinct enzymatic activities that control gating
Reveals novel molecular mechanism that may be a therapeutic target
Generation of Cystic Fibrosis Pigs
Generation of Cystic Fibrosis Pigs
Friday, September 26, 2008
CF pigs
First mammalian disease model other than mice
Provides opportunities to investigate pathogenesis and test new treatments
CF Pigs
CF Pigs Develop Lung Disease
Wednesday, April 28, 2010
CF pigs develop lung disease that mirrors that in humans
Exhibit host-defense defect against bacteria beginning at birth
Resolves chicken and egg conundrum; infection preceeds inflammation
Enables investigation of pathogenesis and therapeutics
CF Ferrets
Generation of Cystic Fibrosis Ferrets
Wednesday, September 1, 2010
CF ferrets
Enable studies of disease mechanisms and new treatments
The ΔF508 mutation causes CFTR misprocessing and cystic fibrosis-like disease in pigs
CF Pigs with ΔF508 Mutation
Wednesday, March 16, 2011
CF pigs with the ΔF508 mutation
Enable studies of therapeutics targeting the common CF mutant
Reduced airway surface pH impairs bacterial killing in the porcine cystic fibrosis lung
Acidic pH Imairs Bacterial Killing in CF
Wednesday, July 4, 2012
CF airway surface liquid is acidic
Acidity inhibits antimicrobials and impairs killing of bacteria
Links loss of CFTR bicarbonate secretion to host defense defect
Increasing airway liquid pH might be beneficial
CF diabetes
CF-Related Diabetes Mellitus in Animal Models
Monday, October 22, 2012
CF ferrets and pigs develop CF-related diabetes mellitus
Provides new opportunity to understand an increasingly frequent complication as people with CF live longer
Defective Mucociliary Transport in CF
Defective Mucociliary Transport in CF
Friday, August 15, 2014
Mucociliary transport is defective in CF beginning at birth
Mucus sometimes fails to detach from submucosal glands, thereby inhibiting mucociliary transport
Results identify new therapeutic strategies
Genomic Signature Approach to Rescue ΔF508-CFTR
Genomic Signature Approach to Rescue ΔF508-CFTR
Monday, September 1, 2014
Develops genomic signature-based approach as novel CF discovery strategy
Identifies small molecules with the potential to rescue ΔF508-CFTR