A5003461736- RNA regulation and disease
- RNA Research and Splicing
- CAR-T cell therapy research
- Glioma Diagnosis and Treatment
- Immune Cell Function and Interaction
- CRISPR and Genetic Engineering
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- T-cell and B-cell Immunology
- Cancer Immunotherapy and Biomarkers
- Virus-based gene therapy research
- Viral Infectious Diseases and Gene Expression in Insects
- RNA Interference and Gene Delivery
- Viral Infections and Immunology Research
- Advanced Electron Microscopy Techniques and Applications
- Radiomics and Machine Learning in Medical Imaging
- Cancer-related molecular mechanisms research
- Electrolyte and hormonal disorders
- Hormonal Regulation and Hypertension
- Immunotherapy and Immune Responses
- COVID-19 Clinical Research Studies
- Hematopoietic Stem Cell Transplantation
- Ion Transport and Channel Regulation
- melanin and skin pigmentation
- Diabetes and associated disorders
University of Bari Aldo Moro
2024-2025
Bambino Gesù Children's Hospital
2017-2025
Istituti di Ricovero e Cura a Carattere Scientifico
2017-2025
Recent studies have reported the emerging role of microRNAs (miRNAs) in human cancers. We systematically characterized miRNA expression and editing brain, which displays highest number A-to-I RNA sites among tissues, de novo glioblastoma brain cancer. identified 299 miRNAs altered their 24 differently edited compared to tissues. focused on site within miR-589-3p seed. MiR-589-3p is a unique almost fully (∼100%) normal with consistent decrease glioblastoma. The version inhibits cell...
N6-methyladenosine (m6A) and adenosine-to-inosine (A-to-I) RNA editing are two of the most abundant modification events affecting adenosines in mammals. Both these modifications determine mRNA fate play a pivotal role tumor development progression.Here, we show that METTL3, upregulated glioblastoma, methylates ADAR1 increases its protein level leading to pro-tumorigenic mechanism connecting YTHDF1, ADAR1. We plays cancer-promoting independently deaminase activity by binding CDK2 mRNA,...
Memory B cells (MBCs) epitomize the adaptation of immune system to environment. We identify two MBC subsets in peripheral blood, CD27dull and CD27bright MBCs, whose frequency changes with age. Heavy chain variable region (VH) usage, somatic mutation replacement-to-silent ratio, CDR3 property changes, reflecting consecutive selection highly antigen-specific, low cross-reactive antibody variants, all demonstrate that MBCs represent sequential developmental stages, stringent antigen-driven...
Abstract Background Paediatric acute myeloid leukaemia (AML) is characterized by poor outcomes in patients with relapsed/refractory disease, despite the improvements intensive standard therapy. The leukaemic cells of paediatric AML show high expression CD123 antigen, and this finding provides biological basis to target chimeric antigen receptor (CAR). However, CAR.CD123 therapy hampered on-target off-tumour toxicity a long “vein-to-vein” time. Methods We developed an off-the-shelf product...
Abstract Chimeric antigen receptor T (CAR-T) cell therapy may achieve long-lasting remission in patients with B-cell malignancies not responding to conventional therapies. However, potentially severe and hard-to-manage side effects, including cytokine release syndrome (CRS), neurotoxicity macrophage activation syndrome, the lack of pathophysiological experimental models limit applicability development this form therapy. Here we present a comprehensive humanized mouse model, by which show...
Adenosine-to-inosine (A-to-I) RNA editing is an essential post-transcriptional mechanism mediated by ADAR enzymes that have been recently associated with cancer. Here, we characterize the inosinome signature in normal brain and de novo glioblastoma (GBM) using new metrics re-stratify GBM patients according to their profiles indicate this event as a possible molecular for sexual dimorphism GBM. We find over 85% of GBMs carry deletion involving genomic locus ADAR3, which specifically expressed...
Adenosine-to-inosine (A-to-I) RNA editing of Alu retroelements is a primate-specific mechanism mediated by adenosine deaminases acting on (ADARs) that diversifies transcriptome changing selected nucleotides in molecules. We tested the hypothesis A-to-I altered rheumatoid arthritis (RA). Synovium expression analysis ADAR1 was investigated 152 RA patients and 50 controls. Peripheral blood mononuclear cells derived from 14 healthy subjects 19 with active at baseline after 12-week treatment were...
Abstract The maintenance of genomic stability requires the coordination multiple cellular tasks upon appearance DNA lesions. RNA editing, post-transcriptional sequence alteration RNA, has a profound effect on cell homeostasis, but its implication in response to damage was not previously explored. Here we show that, breaks, an overall change Adenosine-to-Inosine editing is observed, phenomenon call R NA E diting DA mage esponse (REDAR). REDAR relies checkpoint kinase ATR and recombination...
Immune cell trafficking constitutes a fundamental component of immunological response to tissue injury, but the contribution intrinsic RNA nucleotide modifications this remains elusive. We report that editor ADAR2 exerts tissue- and stress-specific regulation endothelial responses interleukin-6 (IL-6), which tightly controls leukocyte in IL-6-inflamed ischemic tissues. Genetic ablation from vascular cells diminished myeloid rolling adhesion on walls reduced immune infiltration within was...
Massive transcriptome sequencing through the RNAseq technology has enabled quantitative transcriptome-wide investigation of co/post-transcriptional mechanisms such as alternative splicing and RNA editing. The latter is abundant in human transcriptomes which million adenosines are deaminated into inosines by ADAR enzymes. editing modulates innate immune response its deregulation been associated with different diseases including autoimmune inflammatory pathologies, neurodegenerative...
Gene electrotransfer (GET) has recently emerged as an effective nonviral approach for plasmid DNA (pDNA) delivery in gene therapy several pathologies, including cancer. Multiple mechanisms have been identified that influence cell biology after GET, electroporation significantly increases pDNA uptake and immunogenicity, which may directly target death. However, the molecular effects of vivo electroporation-mediated yet to be fully elucidated. In this study, we evaluated transcriptomes murine...
Recent studies have shown that CD32/CD8a/CD28/CD3ζ chimeric receptor cells directly kill breast cancer cells, suggesting the existence of cell surface myeloid FcγR alternative ligands (ALs). Here, we investigated metabolism, ALs, cytotoxicity, and immunoregulatory functions CD64/CD28/CD3ζ in colorectal (CRC) squamous carcinoma head neck. The -SFG retroviral vector was used to produce viruses for T-cell transduction. expansion differentiation were monitored via flow cytometry. Gene expression...
Abstract A-to-I ribonucleic acid (RNA) editing detection is still a challenging task. Current bioinformatics tools rely on empirical filters and whole genome sequencing or exome data to remove background noise, errors, artifacts. Sometimes they make use of cumbersome time-consuming computational procedures. Here, we present REDInet, temporal convolutional network-based deep learning algorithm, profile RNA in human (RNAseq) data. It has been trained REDIportal sites, the largest collection...
Abstract Gene electrotransfer (GET) is an excellent strategy for delivering therapeutic genes and vaccines into the target cell using electric pulses. In view of insights gained during last COVID-19 pandemic, it widely acknowledged that genetic represent a safe affordable option with considerable promise addressing range diseases, including infectious diseases cancer. Growing evidence from preclinical studies clinical trials, which include both intramuscular intratumoral immunotherapy,...
Introduction Immunotherapy with checkpoint inhibitors is an efficient treatment for metastatic melanoma. Development of vitiligo upon immunotherapy represents a specific immune-related adverse event (irAE) diagnosed in 15% patients and associated positive clinical response. Therefore, detailed characterization immune cells during onset melanoma would give insight into the mechanisms mediating both irAE anti-tumor Methods To better understand these aspects, we analyzed T cell subsets from...
Adenosine to inosine (A-to-I) RNA editing is the most frequent event in humans. It converts adenosine double-stranded regions (in coding and non-coding RNAs) through action of deaminase acting on (ADAR) enzymes. Long RNAs, particularly abundant brain, account for a large fraction human transcriptome, their important regulatory role becoming progressively evident both normal transformed cells.Herein, we present bioinformatic analysis generate comprehensive inosinome picture long RNAs...
The SARS-CoV-2 pandemic was defined by the emergence of new variants formed through virus mutation originating from random errors not corrected viral proofreading and/or host antiviral response introducing mutations into genome. While sequencing information hints at cellular RNA editing pathways playing a role in evolution, here, we use an vitro human cell infection model to assess types two strains representing original and alpha variants. showed both different responses patterns with...
<title>Abstract</title> A-to-I RNA editing detection is still a challenging task. Current bioinformatics tools rely on empirical filters and WGS/WES data to remove background noise, sequencing errors, artifacts. Sometimes they make use of cumbersome time-consuming computational procedures. We present here REDInet, TCN-based Deep Learning algorithm, profile in human RNAseq data. It has been trained REDIportal sites, the largest collection changes from > 8000 GTEx REDInet can classify...
A-to-I RNA editing is the most common non-transient epitranscriptome modification. It plays several roles in human physiology and has been linked to disorders. Large-scale deep transcriptome sequencing fostered characterization of at single nucleotide level development dedicated computational resources. REDIportal a unique specialized database collecting ∼16 million putative sites designed face current challenges epitranscriptomics. Its running version enriched with from TCGA project (using...
Epitranscriptomic mechanisms, such as A-to-I RNA editing mediated by ADAR deaminases, contribute to cancer heterogeneity and patients' stratification. enzymes can change the sequence, structure, expression of several RNAs, affecting cell behavior. In glioblastoma, an overall decrease in ADAR2 level/activity has been reported. However, no data on protein levels GBM patient tissues are available; most based ADARs overexpression experiments.We performed IHC analysis correlated survival. We...
Abstract Purpose Patient-derived cancer cell lines can be very useful to investigate genetic as well epigenetic mechanisms of transformation and test new drugs. In this multi-centric study, we performed genomic transcriptomic characterization a large set patient-derived glioblastoma (GBM) stem-like cells (GSCs). Methods 94 (80 I surgery/14 II surgery) 53 (42 surgery/11 GSCs underwent whole exome trascriptome analysis, respectively. Results Exome sequencing revealed TP53 the main mutated gene...