A5008248376- Cystic Fibrosis Research Advances
- Neonatal Respiratory Health Research
- Asthma and respiratory diseases
- Insect and Pesticide Research
- Insect and Arachnid Ecology and Behavior
- Ion channel regulation and function
- Neurobiology and Insect Physiology Research
- Congenital Ear and Nasal Anomalies
- Inhalation and Respiratory Drug Delivery
- Ion Transport and Channel Regulation
- Pharmaceutical studies and practices
- Antimicrobial Peptides and Activities
- Advanced biosensing and bioanalysis techniques
- Healthcare and Venom Research
- Air Quality and Health Impacts
- Genomics and Rare Diseases
- Neurogenetic and Muscular Disorders Research
- Plant and animal studies
- Genomics, phytochemicals, and oxidative stress
- Natural product bioactivities and synthesis
- Neuroscience of respiration and sleep
- Neuroscience and Neuropharmacology Research
- Synthesis and Biological Evaluation
- Phosphodiesterase function and regulation
- Tissue Engineering and Regenerative Medicine
Centre Universitaire Jean-François-Champollion
2021-2024
Université de Toulouse
2024
Université de Poitiers
2010-2022
McGill University
2013-2019
Centre National de la Recherche Scientifique
2010-2013
The most common cystic fibrosis (CF) mutation F508del inhibits the gating and surface expression of CFTR, a plasma membrane anion channel. Optimal pharmacotherapies will probably require both 'potentiator' to increase channel open probability 'corrector' that improves folding trafficking mutant protein its stability at cell surface. Interaction between CF drugs has been reported but remains poorly understood.CF bronchial epithelial cells were exposed corrector VX-809 (lumacaftor) potentiator...
Bicarbonate facilitates mucin unpacking and bacterial killing; however, its transport mechanisms in the airways are not well understood. cAMP stimulates anion efflux through cystic fibrosis (CF) transmembrane conductance regulator (CFTR; ABCC7) channel, this is defective CF. The exchanger pendrin (SLC26A4) also mediates HCO3- upregulated by proinflammatory cytokines. Here, we examined CFTR expression their contributions to secretion human nasal bronchial epithelia. In native tissue, both...
Trikafta, currently the leading therapeutic in cystic fibrosis (CF), has demonstrated a real clinical benefit. This treatment is triple combination therapy of two folding correctors elexacaftor/tezacaftor (VX445/VX661) plus gating potentiator ivacaftor (VX770). In this study, our aim was to compare properties F508del-CFTR cells treated with either lumacaftor (VX809), tezacaftor, elexacaftor, or without ivacaftor. We studied function, maturation and membrane localisation by Ussing chamber...
Cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride (Cl(-)) channel, which plays an important role in physiological anion and fluid secretion, defective several diseases. Although its activation by PKA PKC has been studied extensively, regulation receptors less well understood. To study signaling involved CFTR activation, we measured whole-cell Cl(-) currents BHK cells cotransfected with GPCRs CFTR. In expressing the M3 muscarinic acetylcholine receptor, agonist...
Cystic fibrosis (CF), a genetic disease caused by mutations in the CFTR gene, is life-limiting characterized chronic bacterial airway infection and severe inflammation. Some mutants have reduced responsiveness to cAMP/PKA signaling; hence, pharmacological agents that elevate intracellular cAMP are potentially useful for treatment of CF. By inhibiting breakdown, phosphodiesterase (PDE) inhibitors stimulate vitro vivo. Here, we demonstrate PDE inhibition RPL554, drug has been shown cause...
The cystic fibrosis transmembrane conductance regulator (CFTR) channel is activated by PKA phosphorylation of a regulatory domain that interacts dynamically with multiple CFTR domains and other proteins. large number consensus sequences for has naturally focused most attention on regulation this kinase. We report here human also phosphorylated the tyrosine kinases p60c-Src (proto-oncogene tyrosine-protein kinase) proline-rich kinase 2 (Pyk2), they can cause robust activation quiescent...
Plant extracts are considered as a large source of active biomolecules, especially in phytosanitary and pharmacological fields.
The chloride channel Cystic Fibrosis Transmembrane conductance Regulator (CFTR) is defective in (CF) and mutation of its encoding gene leads to various defects such as retention the misfolded protein endoplasmic reticulum, reduced stability at plasma membrane, abnormal gating with low open probability, thermal instability which inactivation physiological temperature. Pharmacotherapy one major therapeutic approach CF field needs sensible fast tools identify promising compounds. high...
Hymenopterans represent one of the most abundant groups venomous organisms but remain little explored due to difficult access their venom. The development proteo-transcriptomic allowed us explore diversity toxins offering interesting perspectives identify new biological active peptides. This study focuses on U
Ants are among the most abundant terrestrial invertebrate predators on Earth. To overwhelm their prey, they employ several remarkable behavioral, physiological, and biochemical innovations, including an effective paralytic venom. Ant venoms thus cocktails of toxins finely tuned to disrupt physiological systems insect prey. They have received little attention yet hold great promise for discovery novel insecticidal molecules. identify insect-neurotoxins from ant venoms, we screened activity...
The CFTR chloride channel is tightly regulated by phosphorylation at multiple serine residues. Recently it has been proposed that its activity also tyrosine kinases, however the sites remain to be identified. In this study we examined 2 candidate residues near boundary between first nucleotide binding domain and R domain, a region which important for function but devoid of PKA consensus sequences. Mutating tyrosines positions 625 627 dramatically reduced responses Src or Pyk2 without...
Abstract Stinging ants have diversified into various ecological niches, and several evolutionary drivers may contributed to shape the composition of their venom. To comprehend underlying venom variation in ants, we selected 15 Neotropical species recorded a range traits, including ecology, morphology, bioactivity. Principal component analysis both morphological bioactivity traits revealed that stinging display two functional strategies. Additionally, phylogenetic comparative indicated...
Stinging ants have diversified into various ecological niches, and selective pressures may contributed to shape the composition of their venom. To explore drivers underlying venom variation in ants, we sampled 15 South American rainforest species recorded a range traits, including ecology, morphology bioactivities. Principal component analysis both morphological bioactivity traits reveals that stinging display two functional strategies where evolved towards either an exclusively offensive or...
The cystic fibrosis transmembrane conductance regulator (CFTR) is a Cl(-) channel physiologically important in fluid-transporting epithelia and pathologically relevant several human diseases. Here, we show that mutations the C terminus of first nucleotide binding domain comprising latest beta strands (beta(c)5 beta(c)6) influence trafficking, activity, pharmacology CFTR. We mutated CFTR amino acids located beta(c)5-beta(c)6 hairpin, within beta(c)5 strand (H620Q), beta-turn linking two...
One of the major therapeutic strategy in cystic fibrosis aims at developing modulators transmembrane conductance regulator (CFTR) channels. We recently discovered methylglyoxal alpha-aminoazaheterocycle adducts, as a new family CFTR inhibitors. In structure-activity relationship study, we have now identified GPact-11a, compound able not to inhibit but activate CFTR. Here, present effect GPact-11a on activity using vitro (iodide efflux, fluorescence imaging and patch-clamp recordings), ex...
Understanding the functional consequence of rare Cystic Fibrosis (CF) mutations is mandatory for adoption precision therapeutic approaches CF. Here we studied effect very CF mutation, W361R, on CFTR processing and function. We applied western blot, patch clamp pharmacological modulators to study maturation ion transport properties pEGFP-WT mutant constructs, F508del L69H-CFTR, expressed in HEK293 cells. Structural analyses were also performed molecular environment W361 residue. Western blot...
Bicarbonate facilitates mucin unpacking and bacterial killing however its transport mechanisms in the airways are not well understood. cAMP stimulates anion efflux through CFTR (ABCC7) channel this is defective CF. The exchanger pendrin (SLC26A4) also mediates HCO 3 − upregulated by proinflammatory cytokines. Here we examined expression their contributions to secretion human nasal bronchial epithelia. In native tissue, both proteins were most abundant at apical pole of ciliated surface cells...
Introduction: Thirty years after the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene discovery, we are now witnessing wind of change with development second generation modulators targeting CFTR successful marketing first precision medicaments.Areas covered: This review discusses therapeutic options maturation and activity highlight need to better define effects mutations on biology, using a multiclass classification. The contribution new patient-derived cellular models...
Cystic Fibrosis Transmembrane conductance Regulator (CFTR) activation by PKA and PKC has been extensively studied, however its regulation receptors is less well understood. To study signaling upstream of the kinases, we measured whole‐cell Cl‐currents in BHK cells cotransfected with GPCRs CFTR. In expressing M3 muscarinic acetylcholine receptor, agonist carbachol (Cch) caused strong CFTR through two pathways; canonical PKA‐dependent mechanism a second that involves tyrosine phosphorylation....