Cystic Fibrosis Research Advances

Global genomic diversity of Pseudomonas aeruginosa in bronchiectasis

The paper analyzes the genomic diversity of Pseudomonas aeruginosa in bronchiectasis, revealing distinct evolutionary patterns compared to cystic fibrosis and highlighting antimicrobial resistance mechanisms.

The Solute Carrier Family 26 Member 9 Is a Modifier of the Rapidly Progressing Cystic Fibrosis Associated with F508del CFTR Mutations

The paper identifies SLC26A9 variants as modifier genes associated with rapidly progressing cystic fibrosis in patients with deltaF508 homozygous CFTR mutations.

Fecal Dysbiosis and Inflammation in Intestinal-Specific Cftr Knockout Mice on Regimens Preventing Intestinal Obstruction

This study shows that intestinal epithelial-specific loss of CFTR in mice leads to intestinal dysbiosis and inflammation, similar to global Cftr KO mice.

FDA-Approved Drug Screening in Patient-Derived Organoids Demonstrates Potential of Drug Repurposing for Rare Cystic Fibrosis Genotypes

The paper screens 1400 FDA-approved drugs in CF patient-derived intestinal organoids using a functional assay to identify potential repurposing for rare CF genotypes.

Diversity of CFTR variants across ancestries characterized using 454,727 UK biobank whole exome sequences

The paper characterizes CFTR variant diversity across six ancestries using UK Biobank whole exome sequences, identifying ancestry-specific variants and associations with CF-related phenotypes.

Identification of Key Genes and Underlying Mechanisms in Cystic fibrosis and its Associated Complications Based on Bioinformatics Analysis of Next Generation Sequencing Data Analysis

The paper identifies differentially expressed genes and hub genes in cystic fibrosis using NGS data from GEO, revealing potential molecular targets and biomarkers.

Predictive modeling of antibiotic eradication therapy success for new-onset Pseudomonas aeruginosa pulmonary infections in children with cystic fibrosis

The paper uses machine learning to predict antibiotic eradication therapy success for Pseudomonas aeruginosa infections in cystic fibrosis patients based on genomic data, achieving an AUC of 0.87.

K978C CFTR restores essential epithelial function with greater efficiency than wildtype CFTR when expressed in CF airway cells.

This study shows that K978C CFTR, which increases open probability, restores epithelial function more efficiently than wildtype CFTR in CF airway cells when expressed in the presence of CF sputum.

A multimodal iPSC platform for cystic fibrosis drug testing

This study develops an iPSC platform to test CFTR modulators in cystic fibrosis patients with rare mutations, showing genotype-specific responses to drugs.

Single-cell atlas of bronchoalveolar lavage from preschool cystic fibrosis reveals new cell phenotypes

The paper uses scRNA-seq and flow cytometry to identify novel immune and epithelial cell populations in preschool CF patients' bronchoalveolar lavage.

Gene-Specific Nonsense-Mediated mRNA Decay Targeting for Cystic Fibrosis Therapy

This study develops a cocktail of ASOs to specifically increase CFTR W1282X mRNA and protein levels by inhibiting NMD, improving chloride current in human bronchial epithelial cells.

Molecular dynamics and theratyping in airway and gut organoids reveal R352Q-CFTR conductance defect

The paper characterizes the functional and structural defects of the R352Q CFTR mutation using patient-derived organoids and molecular dynamics simulations, showing residual function restored by potentiators but not correctors.

A cystic fibrosis lung disease modifier locus harbors tandem repeats associated with gene expression

The paper identifies VNTRs near SLC9A3 associated with gene expression in CF nasal epithelia and shows their utility in explaining GWAS signals.

CFTR-mediated monocyte-macrophage dysfunction revealed by cystic fibrosis proband-parent comparisons

The paper compares transcriptomic profiles of CF probands and their parents to healthy controls, revealing CFTR-related immune dysfunction in both homozygous and heterozygous carriers.

Cross-kingdom analysis of microbial communities in Cystic Fibrosis and Bronchiectasis

This study analyzes microbial communities in CF and BX patients, finding no significant inter-kingdom interactions between fungal and bacterial communities that impact disease outcomes.

Exon-Skipping Antisense Oligonucleotides for Cystic Fibrosis Therapy

This paper develops an exon-skipping antisense oligonucleotide (ASO) strategy to increase CFTR protein levels in patients with the W1282X mutation by bypassing nonsense-mediated mRNA decay.

In silico and functional characterisation of an ultra-rare CFTR mutation identifies novel lasso motif interactions regulating channel gating

The paper functionally and structurally characterizes an ultra-rare CFTR mutation, showing it responds to specific potentiators and correctors, with altered lasso motif interactions affecting channel gating.

High-throughput functional analysis of CFTR and other apically localized channels in iPSC derived intestinal organoids

The paper describes a high-throughput fluorescence-based assay to measure CFTR and other apical membrane protein activity in iPSC-derived intestinal organoids.

Structural comparative modeling of multi-domain ΔF508 CFTR

The paper uses Rosetta comparative modeling to generate structural models of ΔF508 CFTR and its variants, revealing how the mutation destabilizes the protein and how drugs like VX-809 stabilize it.

A new platform for high-throughput therapy testing on iPSC-derived, immature airway from Cystic Fibrosis Patients

This paper describes a fluorescence-based platform for high-throughput Cystic Fibrosis therapy testing using iPSC-derived immature airway epithelium.

Antisense oligonucleotide-based drug development for Cystic Fibrosis patients carrying the 3849+10kb C-to-T splicing mutation

This study develops an antisense oligonucleotide (ASO) therapy for CF patients with the 3849+10kb C-to-T splicing mutation, showing restoration of CFTR function in patient-derived cells.

Elucidating the phenotypic variability associated with the polyT tract and TG repeats in CFTR

The paper assesses the phenotypic risks of CFTR T5 haplotype variants in individuals without the R117H variant, finding associations with disease severity and penetrance.

CFTR corrector efficacy is associated with occupancy of distinct binding sites

The paper identifies two distinct VX-809 binding sites on CFTR that are critical for corrector efficacy, showing different sensitivity to mutations and allostery.

Topography-dependent gene expression and function of common cell archetypes in large and small porcine airways

The paper compares gene expression and function of airway cell types in small and large porcine airways, finding distinct transcriptomes and functional roles.

Identification of in vivo CFTR conformations during biogenesis and upon misfolding by covalent protein painting (CPP)

This study uses CPP to identify CFTR conformational changes during biogenesis and misfolding, revealing a novel opening mechanism and highlighting the role of the ICL2:NBD2 interface.

Role of transmembrane spanning domain 1 in cystic fibrosis transmembrane conductance regulator folding

This study examines how mutations in the transmembrane spanning domain 1 (TMD1) of CFTR affect its folding and trafficking, showing that some effects are apparent only after TMD2 production.

Microbiome data enhances predictive models of lung function in people with cystic fibrosis

The paper shows that using microbiome data improves predictive models of lung function in cystic fibrosis patients, with non-pathogenic taxa also contributing to predictions.

Mutation of CFAP57 causes primary ciliary dyskinesia by disrupting theasymmetric targeting of a subset of ciliary inner dynein arms

This study identifies mutations in CFAP57 as a cause of primary ciliary dyskinesia by showing they disrupt asymmetric inner dynein arm assembly in cilia.

Antisense oligonucleotide-mediated correction of CFTR splicing improves chloride secretion in cystic fibrosis patient-derived bronchial epithelial cells

This study shows that an antisense oligonucleotide corrects a CFTR splicing mutation in patient-derived cells, improving chloride secretion and outperforming ivacaftor.

Characterization Of Ancestral Origin Of Cystic Fibrosis Of Patients With New Reported Mutations In CFTR

The paper characterizes the ancestral origin of CFTR mutations in Ecuadorian patients, finding high Native American ancestry with exceptions in three individuals with European ancestry.