Center Accomplishments

In addition to current research projects, the CF Research Center has collaborated with researchers from diverse fields and institutions to produce over 170 publications in the past 3 years along with many key findings and 'firsts'

  • First to identify competing SUMO paralog modifications of CFTR that determine WT vs. F508del biogenesis vs. degradation, and recognition of their importance in airway epithelial cells.
  • First to reconstitute selection, ubiquitination and membrane extraction of CFTR in vitro to identify the significant protein interactions and develop small molecules to modulate them.
  • First to identify activation of ENaC activity by neutrophil elastase and bacterial proteases, contributing to airway surface dehydration.
  • First to identify polymorphisms in ENaC subunits that can reduce disease severity in F508del patients.
  • First to apply fluorogen activating proteins (FAPs) to monitor drug rescue of cell surface F508del CFTR and track corrector actions on degradation vs. recycling at the PM, i.e. surface stability of the mutant.
  • First to develop a simultaneous isotopic imaging method to simultaneously monitor in vivo mucociliary clearance and fluid absorption in patient airways.
  • First to recognize vitamin D deficiency as an independent risk factor for Allergic Bronchopulmonary Aspergillosis (ABPA) and to show that Aspergillus-specific Tregs play a role in controlling ABPA.
  • First to show the pathologic roles of IL-23 and IL-17 in CF, leading to discussions/interactions with Constellation Pharma to develop small molecules and Genentech to develop biologics.
  • First to show using RNA-seq of bronchial brushes in CF that type 17 inflammation can be detected in pediatric patients; this inflammation can be quelled by targeting bromodomain proteins. 
  • First to identify a bacterial effector, P. aeruginosa secreted protein (Cif), that blocks pro-resolving lipid pathways to promote inflammation and identified a small molecule to target this factor.
  • First to show that respiratory virus co-infection promotes P. aeruginosa biofilm biogenesis and increased antibiotic resistance.
  • First engineered antimicrobial peptide therapy that reduces infectious burden for both respiratory virus and a highly antibiotic resistant P. aeruginosa biofilm.
  • First use of sodium nitrite to prevent biofilm biogenesis and disrupt P. aeruginosa biofilms, leading to a clinical trial of nitrite in CF patients.
  • First to show the role of a CF microbiota-driven immune response in the development of Distal Intestinal Obstruction Syndrome and cirrhosis.
  • First to show the role of thrombospondin-1 in suppressing neutrophil elastase activity in vivo and inhibiting P. aeruginosa virulence.