A5021455005- Cystic Fibrosis Research Advances
- Neonatal Respiratory Health Research
- Inhalation and Respiratory Drug Delivery
- Advanced biosensing and bioanalysis techniques
- Chronic Lymphocytic Leukemia Research
- Immunodeficiency and Autoimmune Disorders
- Asthma and respiratory diseases
- Lymphoma Diagnosis and Treatment
- Legume Nitrogen Fixing Symbiosis
- Respiratory viral infections research
- Bacterial Genetics and Biotechnology
- Tracheal and airway disorders
- Cutaneous lymphoproliferative disorders research
- Pediatric health and respiratory diseases
- Monoclonal and Polyclonal Antibodies Research
- Synthesis and biological activity
- Pneumocystis jirovecii pneumonia detection and treatment
- Cellular transport and secretion
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- RNA regulation and disease
- Advanced Breast Cancer Therapies
- S100 Proteins and Annexins
- Nuclear Structure and Function
- Congenital Ear and Nasal Anomalies
Istituto Giannina Gaslini
2016-2025
Istituti di Ricovero e Cura a Carattere Scientifico
2018-2024
Watchfrog (France)
2024
University of Modena and Reggio Emilia
2009-2016
Azienda Ospedaliero-Universitaria di Modena
2011
Ospedale Vito Fazzi
2011
Loss-of-function mutations of the CFTR gene cause cystic fibrosis (CF) through a variety molecular mechanisms involving altered expression, trafficking, and/or activity chloride channel. The most frequent mutation among CF patients, F508del, causes multiple defects that can be, however, overcome by combination three pharmacological agents improve channel trafficking and gating, namely, elexacaftor, tezacaftor, ivacaftor. This study was prompted evidence two compound heterozygous for F508del...
We identified a small molecule that, at picomolar concentrations, rescues mutant CFTR chloride channel from protein degradation.
Electrogenic transepithelial ion transport can be measured with the short-circuit current technique. Such experiments are frequently used to evaluate activity of cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-activated chloride channel that is defective in fibrosis, one most frequent genetic diseases. Typically, CFTR estimated from effect CFTRinh-172, selective inhibitor. Unexpectedly, we found addition PPQ-102, another inhibitor, caused only partial inhibition function,...
Abstract Cystic fibrosis (CF) is caused by mutations in the CFTR chloride channel. Deletion of phenylalanine 508 (F508del), most frequent CF mutation, impairs trafficking and gating. F508del-CFTR mistrafficking may be corrected acting directly on mutant itself or modulating expression/activity CFTR-interacting proteins, that thus represent potential drug targets. To evaluate possible candidates for rescue, we screened a siRNA library targeting known interactors. Our analysis identified RNF5...
In recent years, a number of drugs have been approved for the treatment cystic fibrosis (CF). Among them, newly released Trikafta, combination 3 (VX-661/VX-445/VX-770), holds great promise to radically improve quality life large portion patients with CF carrying 1 copy F508del, most frequent transmembrane conductance regulator (CFTR) mutation. Currently available disease-modifying work by rescuing function mutated CFTR anion channel. Recent research has shown that membrane lipids, and cell...
In cystic fibrosis (CF), deletion of phenylalanine 508 (F508del) in the CF transmembrane conductance regulator (CFTR) is associated to misfolding and defective gating mutant channel. One most promising drug targets ubiquitin ligase RNF5, which promotes F508del-CFTR degradation. Recently, first ever reported inhibitor RNF5 was discovered, i.e., 1,2,4-thiadiazol-5-ylidene inh-2. Here, we designed synthesized a series new analogues explore structure–activity relationships (SAR) this class...
Highly homologous B-cell receptors, characterized by non-random combinations of immunoglobulin heavy-chain variable (IGHV) genes and complementarity determining region-3 (HCDR3), are expressed in a recurrent fraction patients affected chronic lymphocytic leukemia (CLL). We investigated the IGHV status 1131 productive IG rearrangements from panel 1126 CLL multicenter Italian study group, correlated presence class HCDR3 stereotyped subsets with major cytogenetic alterations evaluated FISH,...
In cystic fibrosis, deletion of phenylalanine 508 (F508del) in the fibrosis transmembrane conductance regulator (CFTR) anion channel causes misfolding and premature degradation. One possible approach to reducing detrimental health effects could be identification proteins whose suppression rescues F508del-CFTR function bronchial epithelial cells. However, searches for these potential targets have not yet been conducted, particularly a relevant airway background using functional readout. To...
In cystic fibrosis (CF), deletion of phenylalanine 508 (F508del) in the transmembrane conductance regulator (CFTR) anion channel causes misfolding and premature degradation. Considering numerous effects F508del mutation on assembly processing CFTR protein, combination therapy with several pharmacological correctors is likely to be required treat CF patients. Recently, it has been reported that thymosin α-1 (Tα-1) multiple beneficial could lead a single-molecule-based for patients F508del....
S737F is a Cystic Fibrosis (CF) transmembrane conductance regulator (CFTR) missense variant. The aim of our study was to describe the clinical features cohort individuals carrying this In parallel, by exploiting ex vivo functional and molecular analyses on nasal epithelia derived from subset carriers, we evaluated its impact CFTR protein as well responsiveness modulators. We retrospectively collected data all bearing at least one variant followed CF Centre Tuscany region (Italy). Nasal...
Recent studies have described chromosome 2p gain as a recurrent lesion in chronic lymphocytic leukemia (CLL). We investigated the and its relationship with common prognostic biomarkers prospective series of 69 clinical monoclonal B-cell lymphocytosis (cMBL) 218 early stage (Binet A) CLL patients. The was detected by FISH 17 patients (6%, 16 CLL, 1 cMBL) further characterized single nucleotide polymorphism-array. Overall, unfavorable cytogenetic deletions, i.e., del(11)(q23) del(17)(p13) (P =...
The mutation F508del, responsible for a majority of cystic fibrosis cases, provokes the instability and misfolding CFTR chloride channel. Pharmacological recovery F508del-CFTR may be obtained with small molecules called correctors. However, treatment single corrector in vivo vitro only leads to partial rescue, consequence cell quality control systems that still detect as defective protein causing its degradation. We tested effect spautin-1 on since it is an inhibitor USP10 deubiquitinase...
Abstract Peripheral T‐cell lymphomas (PTCLs) comprise a heterogeneous group of neoplasms that are derived from post‐thymic lymphoid cells at different stages differentiation with morphological patterns, phenotypes and clinical presentations. PTCLs highly diverse, reflecting the diverse which they can originate currently sub‐classified using World Health Organization (WHO) 2008 criteria. In 2006 International T‐Cell Lymphoma Project launched Project, building on retrospective study previously...
Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein is expressed at the apical plasma membrane (PM) of different epithelial cells. The most common mutation responsible for onset cystic fibrosis (CF), F508del, inhibits biosynthesis and transport PM, also presents gating stability defects anion channel upon its rescue by use correctors potentiators. This prompted a multiple drug strategy F508delCFTR aimed simultaneously rescue, functional potentiation PM stabilization. Since...
Abstract Introduction N1303K is the fourth most frequent Cystic Fibrosis (CF) causing mutation. People with CF (pwCF) clinical status can be improved by Elexacaftor(ELX)/Tezacaftor(TEZ)/Ivacaftor (ETI) combotherapy. We investigated mechanism underlying N1303K-CFTR rescue. Methods expression and maturation was evaluated Western Blot in cell lines Human Nasal Epithelial Primary Cells (HNECs). Cell surface studied nanoluciferase complementation assay TurboID proximity labeling. Functional...
We broaden the clinical versatility of human nasal epithelial (HNE) cells. HNEs were isolated from 10 participants harboring
The triple combination of elexacaftor/tezacaftor/ivacaftor (ETI) has dramatically improved the outcome people with Cystic Fibrosis (pwCF) at least one F508del mutation. However, carriers rare cystic fibrosis transmembrane conductance regulator (CFTR) variants are not candidates for this innovative treatment.
Introduction Cystic Fibrosis (CF) is a genetic disease due to loss-of-function mutations of the CFTR channel. F508del most frequent mutation (70% alleles in Italy), while other have much lower frequency. Among them, G85E (0.4% frequency globally, 1.13% Italy) emerges as characterized by severe folding and trafficking defect. Methods To investigate pharmacological responsiveness G85E-CFTR variant, we performed functional biochemical characterization heterologous expression systems ex vivo...