A5079593455- Cystic Fibrosis Research Advances
- Neonatal Respiratory Health Research
- Chronic Myeloid Leukemia Treatments
- Protein Tyrosine Phosphatases
- Inhalation and Respiratory Drug Delivery
- Chronic Lymphocytic Leukemia Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Galectins and Cancer Biology
- Acute Lymphoblastic Leukemia research
- PI3K/AKT/mTOR signaling in cancer
- Pancreatic and Hepatic Oncology Research
- Tracheal and airway disorders
- Eosinophilic Disorders and Syndromes
- Bacterial biofilms and quorum sensing
- Immunodeficiency and Autoimmune Disorders
- Spectroscopy Techniques in Biomedical and Chemical Research
- Respiratory viral infections research
- Epigenetics and DNA Methylation
- Cytokine Signaling Pathways and Interactions
- Glycosylation and Glycoproteins Research
- Monoclonal and Polyclonal Antibodies Research
- Glutathione Transferases and Polymorphisms
- Blood disorders and treatments
- Acute Myeloid Leukemia Research
- Antibiotic Resistance in Bacteria
University of Verona
2016-2025
General Department of Preventive Medicine
2015-2022
Boston University
2022
Boston Medical Center
2022
University Hospital Limerick
2019
Rust College
2014
London Health Sciences Centre
2014
In-Q-Tel
2012
University of Bologna
2010
Radboud University Nijmegen
2007
To address the question whether leukocyte integrins are able to generate signals activating neutrophil functions, we investigated capability of mAbs against common beta chain (CD18), or distinct alpha chains CR3, LFA-1, gp150/95, activate respiratory burst. These investigations were performed with bound protein A immobilized tissue culture polystyrene. Neutrophils plated in wells coated anti-CD18 IB4 and 60.3 released H2O2; H2O2 release did not occur when neutrophils an irrelevant,...
This study evaluated the immunoreactivity for bcl-2, a molecule involved in control of programmed cell death, cases pleural (14) and extrapleural (2) solitary fibrous tumour (SFT), malignant mesotheliomas different histological types, variety CD34-positive CD34-negative spindle-cell tumours. In all SFTs, strong diffuse immunostaining was demonstrated with anti-bel-2 antibody, sharply contrasting complete lack staining observed mesotheliomas. The specificity immunodetection bcl-2 SFT...
Stimulation of adherent human neutrophils (PMN) with tumor necrosis factor (TNF) triggers protein tyrosine phosphorylation (Fuortes, M., W. Jin, and C. Nathan. 1993. J. Cell Biol. 120:777-784). We investigated the dependence this response on beta 2 integrins by using PMN isolated from a leukocyte adhesion deficiency (LAD) patient, which do not express integrins, plating surface bound anti-beta (CD18) antibodies. Protein increased in plated fibrinogen was enhanced TNF. Triggering did occur...
The ALLI gene, located at chromosome band 11q23, is involved in acute leukemia through a series of translocations and fusion to variety genes, most frequently A4 AF9. fused genes encode chimeric proteins proteins. Because the Drosophila homologue ALL1, trithorax, positive regulator homeotic acts level transcription, it conceivable that alterations ALL1 transcriptional activity may underlie its action malignant transformation. To begin studying this, we examined All1, AF4, AF9, AF17 for...
The purpose of this study is to identify novel proteins released by cancer cells that are involved in extracellular matrix (ECM) remodeling using small-volume samples and automated technology. We applied multidimensional protein identification technology (MudPIT), which incorporates two-dimensional capillary chromatography coupled tandem mass spectrometry small quantities serum-free supernatants resting or phorbol ester-activated Suit-2 pancreatic cells. Selected markers were validated...
Abstract Ag presentation by dendritic cells (DC) is essential to effective antitumor T cell responses in cancer patients. Depending on their origin, maturation state, and the ambient cytokine milieu, DC can differentiate into distinct subpopulations, which preferentially either induce Th1 activation (CD11c+,CD123− myeloid (MDC)) or immunosuppressive development (CD11c−,CD123+ plasmacytoid (PDC)). The present study was undertaken characterize effects of pancreatic carcinoma cell-derived...
Cystic fibrosis (CF) is a common genetic disease caused by mutations of the cystic transmembrane conductance regulator (CFTR) gene. Persistent lung inflammation, characterized increasing polymorphonuclear leukocyte recruitment, major cause decline in respiratory function patients with CF and leading morbidity mortality. CFTR expressed various cell types, including leukocytes, but its involvement regulation recruitment unknown.We evaluated whether leukocytes might present alterations adhesion...
Despite the promising results of new CFTR targeting drugs designed for recovery F508del- and class III variants activity, none them have been approved individuals with selected rare mutations, because uncharacterized lack information associated ability these compounds in recovering their molecular defects. Here we used both rectal organoids (colonoids) primary nasal brushed cells (hNEC) derived from a CF patient homozygous A559T (c.1675G>A) variant to evaluate responsiveness this pathogenic...
We tested the hypothesis that human polymorphonuclear leukocytes (PMN), bearing complement receptors CR1 and CR3, might also synthesize C3, particularly when activated by LPS or cytokines. Northern blot analysis of total RNA, obtained from purified PMN stimulated overnight with cytokines (IFN-gamma, TNF-alpha, IL-1) showed 5.3-kb RNA transcript reported for C3 in hepatocytes monocytes. No transcripts C4 factor B were detected. Time course studies mRNA expression treated TNF-alpha...
The ALL-1 gene positioned at 11q23 is directly involved in human acute leukemia either through a variety of chromosome translocations or by partial tandem duplications. the homologue Drosophila trithorax which plays critical role maintaining proper spatial and temporal expression Antennapedia - bithorax homeotic genes determining fruit fly’s body pattern. Utilizing specific antibodies, we found that protein distributes cultured cells nuclear punctate Several chimeric proteins encoded...
Background Evaluation of cystic fibrosis transmembrane conductance regulator (CFTR) functional activity to assess new therapies and define diagnosis (CF) is cumbersome. It known that leukocytes express detectable levels CFTR but the molecule has not been characterized in these cells. In this study we aim at setting up validating a blood test evaluate expression function leukocytes. Description Western blot, PCR, immunofluorescence cell membrane depolarization analysis by single-cell...
We have developed a humanized bi-specific T-cell engager (BiTE) targeting receptor tyrosine kinase-like orphan 1 (ROR1), cell surface antigen present on range of malignancies and cancer-initiating cells. Focusing initially pancreatic cancer, we demonstrated that our ROR1 BiTE results in T mediated antigen-specific cytotoxicity against ROR1-expressing cancer lines vitro at exceedingly low concentrations (0.1 ng/mL) effector to target ratios. Our prevented engraftment tumor xenografts murine...
People with cystic fibrosis should be considered at increased risk of developing severe symptoms COVID-19. Strikingly, a broad array evidence shows reduced spread SARS-CoV-2 in these subjects, suggesting potential role for CFTR the regulation infection/replication. Here, we analyzed replication wild-type and CFTR-modified human bronchial epithelial cell lines primary cells to investigate infection people fibrosis. Both immortalized expressing wt or F508del-CFTR along CRISPR/Cas9 CFTR-ablated...
The effect of presently available CFTR modulator combinations, such as elexacaftor (ELX), tezacaftor (TEZ), and ivacaftor (IVA), on rare alleles is often unknown. Several assays have been developed, forskolin-induced swelling (FIS), to evaluate the rescue uncommon both by established novel modulators in patient-derived primary cell cultures (organoids). Presently, we assessed CFTR-mediated electrical current across rectal organoid-derived epithelial monolayers. This technique, which allows...
Several reports have indicated that SARS-CoV-2 infection displays unexpected mild clinical manifestations in people with cystic fibrosis (pwCF), suggesting CFTR expression and function may be involved the life cycle. To evaluate possible association of activity replication, we tested antiviral two well-known inhibitors (IOWH-032 PPQ-102) wild type (WT)-CFTR bronchial cells. replication was inhibited by IOWH-032 treatment, an IC50 4.52 μM, PPQ-102, 15.92 μM. We confirmed this effect on...
Cystic fibrosis (CF) is caused by mutation of the CFTR gene, encoding an epithelial anion channel. Here we evaluated effect modulator combination elexacaftor-tezacaftor-ivacaftor (ETI) on function four rare, poorly characterized variants: L383S, I507del, L1065P and R1066H. Intestinal organoids were obtained from subjects carrying variants or R1066H in trans a minimal allele (class I mutation). Organoids monolayers used to assess ETI protein abundance CFTR-mediated chloride, bicarbonate,...
Cystic fibrosis (CF) is a life-shortening autosomal recessive disease, caused by loss-of-function mutations that affect the CF transmembrane conductance regulator (CFTR) anion channel. G542X second-most common CF-causing variant, and it does not respond to current CFTR modulator drugs. Our study explores use of adenine base editing edit non-CF-causing G542R, recover function. Using editor engineered virus-like particles (BE-eVLPs) in patient-derived intestinal organoids, we achieved ∼2%...
Cystic fibrosis (CF) is a genetic disease caused by mutations in the CF transmembrane conductance regulator ( CFTR ) gene, leading to chronic, unresolved inflammation of airways due uncontrolled recruitment polymorphonuclear leukocytes (PMNs). Evidence indicates that loss‐of‐function, addition promoting pro‐inflammatory phenotype, associated with an increased risk developing cancer, suggesting can exert tumor‐suppressor functions. Three‐dimensional (3D) vitro culture models, such as lung...
Aimed at developing accurate, reliable and cost-saving analytical techniques for drugs screening we evaluated the potential of Fourier Transform (FT) InfraRed (IR) microspectroscopy (microFTIR) as a quantitative pre-diagnostic approach rapid identification IR signatures targeting specific molecular pathways causing Chronic Myeloid Leukemia (CML). To obtain reproducible FTIR absorbance spectra necessary spatial resolution optimized sample preparation acquisition parameters on single channel...