A5016888981- Acute Myeloid Leukemia Research
- RNA Research and Splicing
- Protein Degradation and Inhibitors
- RNA Interference and Gene Delivery
- MicroRNA in disease regulation
- RNA modifications and cancer
- CAR-T cell therapy research
- Nuclear Structure and Function
- Ion channel regulation and function
- Hearing, Cochlea, Tinnitus, Genetics
- Erythrocyte Function and Pathophysiology
- Acute Lymphoblastic Leukemia research
- Immune Cell Function and Interaction
- Advanced biosensing and bioanalysis techniques
- RNA and protein synthesis mechanisms
- Plant Disease Resistance and Genetics
- Chromosomal and Genetic Variations
- Histone Deacetylase Inhibitors Research
- Genetic and Environmental Crop Studies
- Genomic variations and chromosomal abnormalities
- Cystic Fibrosis Research Advances
- Ear Surgery and Otitis Media
- Genetic Associations and Epidemiology
- Extracellular vesicles in disease
- Endoplasmic Reticulum Stress and Disease
IRCCS Materno Infantile Burlo Garofolo
2010-2024
University of Perugia
2019-2024
University of Trieste
2024
International Centre for Genetic Engineering and Biotechnology
2013-2020
Boston University
2019
Seattle University
2019
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...
NPM1 is the most frequently mutated gene in adults with acute myeloid leukemia (AML). The interaction between mutant (NPM1c) and exportin-1 (XPO1) causes aberrant cytoplasmic dislocation of NPM1c promotes high expression homeobox (HOX) genes, which critical for maintaining leukemic state NPM1-mutated cells. Although there a rationale using XPO1 inhibitors AML, selinexor administered once or twice per week did not translate into clinical benefit patients mutations. Here, we show that this...
Abstract Familial dysautonomia (FD) is a rare genetic disease with no treatment, caused by an intronic point mutation (c.2204+6T>C) that negatively affects the definition of exon 20 in elongator complex protein 1 gene (ELP1 also known as IKBKAP). This substitution modifies 5′ splice site and, combination regulatory splicing factors, induces different levels skipping, various tissues. Here, we evaluated therapeutic potential novel class U1 snRNA molecules, exon-specific U1s (ExSpeU1s),...
Spinal Muscular Atrophy results from loss-of-function mutations in SMN1 but correcting aberrant splicing of SMN2 offers hope a cure. However, current splice therapy requires repeated infusions and is expensive. We previously rescued SMA mice by promoting the inclusion defective exon with germline expression Exon-Specific U1 snRNAs (ExspeU1). Here we tested viral delivery ExspeU1s encoded adeno-associated virus AAV9. Strikingly increased 7 SMN protein levels phenotype mild severe mice. In...
Acute myeloid leukemia (AML) still represents an unmet clinical need for adult and pediatric patients. Adoptive cell therapy by chimeric antigen receptor (CAR)-engineered T cells demonstrated a high therapeutic potential, but further development is required to ensure safe durable disease remission in AML, especially elderly To date, translation of CAR T-cell AML limited the absence ideal tumor-specific antigen. CD123 CD33 are 2 most widely overexpressed leukemic stem biomarkers their shared...
Abstract Inner ear organoids derived from differentiation of human pluripotent stem cells have recently gained momentum as tools to study inner development and developmental defects. An additional exciting aspect about this technology is represented by its translational potential, specifically, the use validate therapeutics for hearing balance restoration on human/patient-specific cells. This latter will be briefly discussed here including opportunities current limitations.
Half of the human genome is derived from Transposable Elements (TEs), among which Alu, LINE-1 and SVA are particularly represented. Germline transposition TEs generates polymorphisms between individuals may be used to study association with phenotypes inter-individual differences. Italy presents an increased number isolated villages compared other European groups, these isolates provide a desirable subject understand genetic variability Italian peninsula. Therefore, we focused on polymorphic...
-mutated acute myeloid leukemia (AML) is the most frequent AML subtype. As wild-type NPM1 known to orchestrate ribosome biogenesis, it has been hypothesized that altered translation may contribute leukemogenesis and maintenance in
Dual molecular diagnoses are defined as the presence of pathogenic variants at two distinct and independently segregating loci that cause different Mendelian conditions. In this study, we report identification double genetic disorders in a series patients with complex clinical features. last 24 months, 342 syndromic have been recruited clinically characterised. Whole Exome Sequencing analysis has performed on proband both parents identified seven affected by dual diagnosis. Upon detailed...
We have explored the functional relationships between spliceosome and Microprocessor complex activities in a novel class of microRNAs (miRNAs), named Splice site Overlapping (SO) miRNAs, whose pri-miRNA hairpins overlap splice sites. focused on evolutionarily conserved SO miR-34b, we identified two indispensable elements for recognition its 3′ site: branch point located hairpin downstream purine-rich exonic splicing enhancer. In minigene systems, inhibition owing to enhancer deletion or AG...
Recurrent loss-of-function mutations of BCL6 co-repressor (BCOR) gene are found in about 4% AML patients with normal karyotype and associated DNMT3a poor prognosis. Therefore, new anti-leukemia treatments mouse models needed for this combinatorial genotype. For purpose, we first generated a Bcor-/- knockout model characterized by impaired erythroid development (macrocytosis anemia) enhanced thrombopoiesis, which both features myelodysplasia/myeloproliferative neoplasms. We then created...
MicroRNAs are found throughout the genome and processed by microprocessor complex (MPC) from longer precursors. Some precursor miRNAs overlap intron:exon junctions. These s plice site o verlapping microRNAs (SO-miRNAs) mostly located in coding genes. It has been intimated, rarer examples of SO-miRNAs noncoding RNAs, that competition between spliceosome MPC modulates alternative splicing. However, effect this on transcripts is unknown. Unexpectedly, we show neither Drosha silencing nor SF3b1...
In cystic fibrosis (CF), the correction of splicing defects represents an interesting therapeutic approach to restore normal CFTR function. this study, we focused on 10 common mutations/variants 711+3A>G/C, 711+5G>A, TG13T3, TG13T5, TG12T5, 1863C>T, 1898+3A>G, 2789+5G>A, and 3120G>A that induce skipping corresponding exons 5, 10, 13, 16, 18. To rescue tested, in a minigene assay, panel modified U1 small nuclear RNAs (snRNAs), named Exon Specific U1s (ExSpeU1s), was engineered bind intronic...
Objective: Hearing loss (HL) is the most common form of sensory impairment, affecting millions individuals worldwide. Pre-lingual non-syndromic hearing present in 1 700 children and half cases impairment caused by genetic factors. Methods: We analysed an Italian family with a bilateral sensorineural HL several members inherited autosomal dominant manner. To perform linkage study, subjects were genotyped high density SNP arrays. Parametric analysis using Merlin detected significant 40-Mb...
<title>Abstract</title> Background A significant fraction of mammalian genomes is derived from transposable element (TE) sequences, constituting about half the human genome, in which retrotransposons such as Alu, LINE-1 and SVA are particularly represented some them also have functional roles. Germline transposition these elements generates polymorphisms between individuals may be used to study association with phenotypes, inter-individual differences natural selection. Italy presents an...