A5073453050- Congenital gastrointestinal and neural anomalies
- Medical Imaging and Pathology Studies
- Heterotopic Ossification and Related Conditions
- Parathyroid Disorders and Treatments
- Cystic Fibrosis Research Advances
- Neonatal Respiratory Health Research
- Ion channel regulation and function
- Digestive system and related health
- Neuroscience and Neuropharmacology Research
- Renal and related cancers
- Cholinesterase and Neurodegenerative Diseases
- RNA regulation and disease
- Retinoids in leukemia and cellular processes
- Neuroscience of respiration and sleep
- Vitamin C and Antioxidants Research
- RNA Research and Splicing
- Hereditary Neurological Disorders
- Erythrocyte Function and Pathophysiology
- Genomics and Chromatin Dynamics
- Renal Diseases and Glomerulopathies
- Mitochondrial Function and Pathology
- RNA and protein synthesis mechanisms
- Congenital Anomalies and Fetal Surgery
- Inflammasome and immune disorders
- Parallel Computing and Optimization Techniques
University of Genoa
2012-2022
Istituto Giannina Gaslini
2011-2021
Istituti di Ricovero e Cura a Carattere Scientifico
2002-2019
University of Pisa
1996-2017
Bambino Gesù Children's Hospital
2017
Medical Genetics Center
2000-2017
University of Milan
2013
Humanitas University
2013
Laboratory of Molecular Genetics
2000-2012
Columbia University
2009
Calcium-dependent chloride channels are required for normal electrolyte and fluid secretion, olfactory perception, neuronal smooth muscle excitability. The molecular identity of these membrane proteins is still unclear. Treatment bronchial epithelial cells with interleukin-4 (IL-4) causes increased calcium-dependent channel activity, presumably by regulating expression the corresponding genes. We performed a global gene analysis to identify that regulated IL-4. Transfection specific small...
May-Hegglin anomaly, Sebastian syndrome, Fechtner and Epstein syndrome are autosomal dominant macrothrombocytopenias distinguished by different combinations of clinical laboratory signs, such as sensorineural hearing loss, cataract, nephritis, polymorphonuclear Döhle-like bodies. Mutations in the MYH9 gene encoding for nonmuscle myosin heavy chain IIA (NMMHC-IIA) have been identified all these syndromes. To understand role mutations, we report molecular defects 12 new cases, which together...
Expression of TMEM16A protein is associated with the activity Ca(2+)-activated Cl(-) channels. primary transcript undergoes alternative splicing. thus resulting in generation multiple isoforms. We have determined pattern splicing and assessed functional properties corresponding variants. found three exons, 6b, 13, 15, coding for segments 22, 4, 26 amino acids, respectively, which are differently spliced human organs. By patch clamp experiments on transfected cells, we that skipping exon 6b...
The TMEM16A protein has a potential role as Ca(2+)-activated Cl(-) channel (CaCC) in airway epithelia where it may be important the homeostasis of surface fluid. We investigated function and expression primary human bronchial epithelial cells cell line (CFBE41o-). Under resting conditions, was relatively low. However, silencing with short-interfering RNAs caused marked inhibition CaCC activity, thus demonstrating that low is sufficient to support Ca(2+)-dependent transport. Following...
Congenital abnormalities of the kidney and urinary tract are most common cause pediatric failure. These disorders highly heterogeneous, etiologic factors poorly understood.We performed genomewide linkage analysis whole-exome sequencing in a family with an autosomal dominant form congenital or (seven affected members). We also sequence 311 unrelated patients, as well histologic functional studies.Linkage identified five regions genome that were shared among all members. Exome single, rare,...
Abstract Objective To explore tumor necrosis factor (TNF)–induced apoptosis in neutrophils from patients with TNF receptor–associated periodic syndrome (TRAPS) and to correlate the results different kinds of TNFRSF1A mutations. Methods Two hundred sixty‐five clinically suspected inherited autoinflammatory were screened for mutations gene. Neutrophils isolated heparinized blood by dextran sedimentation incubated without cycloheximide (CHX) TNFα. Cell was assessed human annexin V binding,...
SCN(-) (thiocyanate) is an important physiological anion involved in innate defense of mucosal surfaces. oxidized by H(2)O(2), a reaction catalyzed lactoperoxidase, to produce OSCN(-) (hypothiocyanite), molecule with antimicrobial activity. Given the importance availability airway surface fluid, we studied transepithelial transport human bronchial epithelium. We found evidence for at least three mechanisms basolateral apical flux. cAMP and Ca(2+) regulatory pathways controlled through cystic...
Understanding the molecular mechanisms that underlie regulation of transcription human osteopontin encoding gene (OPN) may help to clarify several processes, such as fibrotic evolution organ damage, tumorigenesis and metastasis, immune response, in which OPN overexpression is observed. With aim evaluate variants with functional effect on transcription, we have analyzed promoter region focused our investigation three common present first 500 bp upstream start site. Transfection constructs...
Abstract Recent data show that proinflammatory stimuli may modify significantly ion transport in the airway epithelium and therefore properties of surface fluid. We have studied effect IL-4, a cytokine involved pathogenesis asthma, on transepithelial human bronchial vitro. Incubation polarized epithelial cells with IL-4 for 6–48 h causes marked inhibition amiloride-sensitive Na+ channel as measured short circuit current experiments. On other hand, evokes 2-fold increase activated by cAMP...
Longitudinal bone growth is determined by the process of endochondral ossification in cartilaginous plate, which located at both ends vertebrae and long bones involves many systemic hormones local regulators. We report molecular characterization a de novo balanced t(2;7)(q37.1;q21.3) translocation young female with Marfanoid habitus skeletal anomalies. The was characterized fluorescence situ hybridization (FISH), checked for other abnormalities array-comparative genomic (CGH), finally,...
CFTR (cystic fibrosis transmembrane conductance regulator) is an epithelial Cl- channel inhibited with high affinity and selectivity by the thiazolidinone compound CFTR(inh)-172. In present study, we provide evidence that CFTR(inh)-172 acts directly on CFTR. We introduced mutations in amino acid residues of sixth helix protein, a domain has important role formation pore. Basic hydrophilic acids at positions 334-352 were replaced alanine sensitivity to was assessed using functional assays....
TMEM16F is a membrane protein with possible dual function as an ion channel and phospholipid scramblase. The properties of channels associated the link between scramblase activity are matter debate. We studied four isoforms generated by alternative splicing. Upregulation three or silencing endogenous increased decreased, respectively, both activities. Introduction activating mutation in sequence caused marked increase phosphatidylserine scrambling transport indicating direct involvement...
Abstract Goblet cell hyperplasia, a feature of asthma and other respiratory diseases, is driven by the Th-2 cytokines IL-4 IL-13. In human bronchial epithelial cells, we find that induces expression many genes coding for ion channels transporters, including TMEM16A, SLC26A4, SLC12A2, ATP12A. At functional level, enhances calcium- cAMP-activated chloride/bicarbonate secretion, resulting in high bicarbonate concentration alkaline pH fluid covering apical surface epithelia. Importantly, mucin...
Objectives Tumour necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS) is caused by TNFRSF1A mutations, known to induce intracellular retention of the TNFα receptor 1 (TNFR1) protein, defective TNFα-induced apoptosis, and production reactive oxygen species. As downregulation autophagy, main cellular pathway involved in insoluble aggregate elimination, has been observed increase inflammatory response, we investigated whether it plays a role TRAPS pathogenesis. Methods The...
<h3>Objectives</h3> Systemic auto-inflammatory disorders (SAIDs) are a heterogeneous group of monogenic diseases sharing primary dysfunction the innate immune system. More than 50% patients with SAID does not show any mutation at gene(s) tested because lack precise clinical classification criteria and/or incomplete gene screening. To improve molecular diagnosis and genotype interpretation SAIDs, we undertook development next-generation sequencing (NGS)-based protocol designed to simultaneous...
Lysyl oxidase is an extracellular enzyme that controls the maturation of collagen and elastin. III often show similar expression patterns in fibrotic tissues. Therefore, we investigated influence lysyl overexpression on promoter activity human COL3A1 gene. Our results showed when COS-7 cells overexpressed mature form oxidase, was increased up to average 12 times tested by luciferase reporter assay. The effect specific, because other promoters were not affected. Moreover, abolished...
In this report, we present a fluorescencebased approach to the assessment of cellular gene expression and transcription rates. Nuclear run-on was performed by supplying biotin-16-UTP nuclei, labeled transcripts were bound streptavidin-coated magnetic beads. Total cDNA then synthesized means random hexamer primed reverse captured molecules. To monitor transcript abundance in cDNA, both from nuclear total RNA, propose semiquantitative PCR based on use fluorescent primers.
Congenital central hypoventilation syndrome (CCHS) is a rare neurocristopathy characterized by absence of adequate autonomic control respiration with decreased sensitivity to hypoxia and hypercapnia. Frameshift mutations polyalanine triplet expansions in the coding region PHOX2B have been identified vast majority CCHS patients correlation between length expanded severity has reported. In this work, we undertaken vitro analyses aimed at identifying pathogenetic mechanisms which underlie...
Abstract Lactoferrin, a single chain cationic glycoprotein, present in the secondary granules of neutrophils, acts as negative feedback regulator myelopoiesis. Specific receptors for lactoferrin were detected on surface different hematopoietic cell types. The influence growth culture has been reported. Interactions with DNA also demonstrated. In paper we confirm presence specific binding sites K562 cells and estimate number dissociation constant. By Western blotting analysis performed...