A5043645480- Epigenetics and DNA Methylation
- Cancer-related molecular mechanisms research
- Histone Deacetylase Inhibitors Research
- MicroRNA in disease regulation
- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- Glioma Diagnosis and Treatment
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Radiomics and Machine Learning in Medical Imaging
- Ubiquitin and proteasome pathways
- Machine Learning in Bioinformatics
- Protein Degradation and Inhibitors
- Cancer Genomics and Diagnostics
- CAR-T cell therapy research
- Calibration and Measurement Techniques
- Cancer, Hypoxia, and Metabolism
- RNA Research and Splicing
- Particle Accelerators and Free-Electron Lasers
- Occupational and environmental lung diseases
- Extracellular vesicles in disease
- Circular RNAs in diseases
- Algorithms and Data Compression
- Genomics and Phylogenetic Studies
- interferon and immune responses
Biogem
2020-2025
Sylvester Comprehensive Cancer Center
2023-2025
University of Miami
2023-2025
University of Naples Federico II
2020-2024
University of Siena
2022
National Research Council
2022
Fondazione IRCCS Istituto Nazionale dei Tumori
2022
Information Technology University
2021
University of Sannio
2017-2020
Association with hypomethylating agents is a promising strategy to improve the efficacy of immune checkpoint inhibitors-based therapy. The NIBIT-M4 was phase Ib, dose-escalation trial in patients advanced melanoma agent guadecitabine combined anti-CTLA-4 antibody ipilimumab that followed traditional 3 + design (NCT02608437). Patients received 30, 45 or 60 mg/m2/day subcutaneously on days 1 5 every weeks starting week 0 for total four cycles, and mg/kg intravenously day cycles. Primary...
Sampling restrictions have hindered the comprehensive study of invasive non-enhancing (NE) high-grade glioma (HGG) cell populations driving tumor progression. Here, we present an integrated multi-omic analysis spatially matched molecular and multi-parametric magnetic resonance imaging (MRI) profiling across 313 multi-regional biopsies, including 111 from NE, 68 HGG patients. Whole exome RNA sequencing uncover unique genomic alterations to unresectable NE tumor, subclonal events, which inform...
It is currently unknown how many RNA transcripts are able to induce degradation of microRNAs (miRNA) via the mechanism known as target-directed miRNA (TDMD). We developed TDMDfinder, a computational pipeline that identifies 'high confidence' TDMD interactions in Human and Mouse transcriptomes by combining sequence alignment feature selection approaches. Our predictions suggested widespread, with potentially every controlled endogenous targets. experimentally tested 37 TDMDfinder predictions,...
Brain-derived neurotrophic factor (BDNF) plays a pivotal role in neuronal growth and differentiation, plasticity, learning, memory. Using CRISPR/Cas9 technology, we generated vital Bdnf null mutant line zebrafish carried out its molecular behavioral characterization. Although no defects are evident on morphological inspection, 66% of coding genes 37% microRNAs turned to be differentially expressed bdnf-/- compared with wild type sibling embryos. We deeply investigated the circadian clock...
Abstract Background Glioblastoma multiforme (GBM) is a highly aggressive primary brain tumor, that refractory to standard treatment and immunotherapy with immune-checkpoint inhibitors (ICI). Noteworthy, melanoma metastases (MM-BM), share the same niche as GBM, frequently respond current ICI therapies. Epigenetic modifications regulate GBM cellular proliferation, invasion, prognosis may negatively cross-talk between malignant cells immune in tumor milieu, likely contributing limit efficacy of...
The biological and clinical relevance of the DNA methylation landscape in metastatic melanoma (MM) remains underexplored. In a retrospective cohort 191 MM lesions from 165 AJCC Stage III IV patients (EPICA cohort) we identified four tumor subsets (i.e. DEMethylated, LOW, INTermediate CIMP) with progressively increasing levels methylation. These findings were validated TCGA MM. EPICA, LOW tumors exhibited significantly longer survival lower progression rate to more advanced stages, compared...
Abstract Background Co-targeting of immune checkpoint inhibitors (ICI) CTLA-4 and PD-1 has recently become the new first-line standard care therapy pleural mesothelioma (PM) patients, with a significant improvement overall survival (OS) over conventional chemotherapy. The analysis by tumor histotype demonstrated greater efficacy ICI compared to chemotherapy in non-epithelioid (non-E) vs. epithelioid (E) PM, although some E PM patients also benefit from treatment. This evidence suggests that...
Viral mimicry refers to the activation of innate antiviral immune responses due induction endogenous retroelements (REs). augments antitumor and sensitizes solid tumors immunotherapy. Here, we found that targeting what believe be a novel, master epigenetic regulator, Zinc Finger Protein 638 (ZNF638), induces viral in glioblastoma (GBM) preclinical models potentiates checkpoint inhibition (ICI). ZNF638 recruits HUSH complex, which precipitates repressive H3K9me3 marks on REs. In GBM, is...
Background: co-targeting of immune checkpoint inhibitors (ICI) CTLA-4 and PD-1 has recently become the new first-line standard care therapy pleural mesothelioma (PM) patients, with a significant improvement overall survival (OS) over conventional chemotherapy. The analysis by tumor histotype demonstrated greater efficacy ICI therapy, compared to chemotherapy, in non-epithelioid (non-E) vs. epithelioid (E) PM, although some E PM patients also benefit from treatment. This evidence suggests...
Long non-coding RNAs (lncRNAs) represent a novel class of having crucial role in many biological processes. The identification long homologs among different species is essential to investigate such roles model organisms as homologous genes tend retain similar molecular and functions. Alignment–based metrics are able effectively capture the conservation transcribed coding sequences then homology protein genes. However, unlike poor sequence makes their challenging task. In this study we...
Small non-coding RNAs (ncRNAs) are short sequences involved in gene regulation many biological processes and diseases. The lack of a complete comprehension their functionality, especially genome-wide scenario, has demanded new computational approaches to annotate roles. It is widely known that secondary structure determinant know RNA function machine learning based have been successfully proven predict from information. Here we show can be predicted with good accuracy lightweight...
Embryonic stem cells (ESCs) are derived from inner cell mass (ICM) of blastocyst. In serum/LIF culture condition, they show variable expression pluripotency genes that mark fluctuation between and differentiation metastate. The ESCs subpopulation marked by zygotic genome activation gene (ZGA) signature, including Zscan4, retains a wider potency than epiblast-derived ESCs. We have recently shown retinoic acid (RA) significantly enhances Zscan4 population. However, it remains unexplored how RA...
Improvement of efficacy immune checkpoint blockade (ICB) remains a major clinical goal. Association ICB with immunomodulatory epigenetic drugs is an option. However, inhibitors show heterogeneous landscape activities. Analysis transcriptional programs induced in neoplastic cells by distinct classes may foster identification the most promising agents. Melanoma cell lines, characterized for mutational and differentiation profile, were treated DNA methyltransferases (guadecitabine), histone...
Melanoma is the deadliest form of skin cancer and metastatic disease associated with a significant survival rate drop. There an urgent need for consistent tumor biomarkers to scale precision medicine reduce mortality. Here, we aimed identify melanoma-specific circulating microRNA signature assess its value as diagnostic tool.The study consisted discovery phase two validation phases. Circulating plasma extracellular vesicles (pEV) profiles were obtained from cohort melanoma patients normal...
Abstract Purpose/methods The determination of tumour biomarkers is paramount to advancing personalized medicine, more so in rare tumours like medullary thyroid carcinoma (MTC), whose diagnosis still challenging. aim this study was identify non-invasive circulating MTC. To achieve goal, paired MTC tissue and plasma extracellular vesicle samples were collected from multiple centres microRNA (miRNA) expression levels evaluated. Results a discovery cohort 23 patients analysed using miRNA arrays....
The unveiling of long non-coding RNAs as important gene regulators in many biological contexts has increased the demand for efficient and robust computational methods to identify novel from transcripts assembled with high throughput RNA-seq data. Several classes sequence-based features have been proposed distinguish between coding transcripts. Among them, open reading frame, conservation scores, nucleotide arrangements, RNA secondary structure used success literature recognize intergenic...
MicroRNAs (miRNAs) are involved in post-transcriptional gene expression regulation and mechanisms of cancer growth metastases. In this light, miRNAs could be promising therapeutic targets biomarkers clinical practice. Therefore, we investigated if specific their target genes contribute to laryngeal squamous cell carcinoma (LSCC) development. We found a significant decrease miR-449a LSCC patients with nodal metastases (63.3%) compared without involvement (44%). The AmpliSeq Transcriptome...
Coronavirus disease 2019 (COVID-19) emerged in December when the first case was reported Wuhan, China, and turned into a pandemic. Whole-genome sequencing (WGS) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays crucial role understanding disease. For this reason, we performed WGS 101 SARS-CoV-2 strains obtained from individuals two districts Campania (Italy) January to May 2021. The phylogenetic analysis sequence data identified five types clades including 10 different...
Abstract Non-coding RNAs (ncRNAs) are small non-coding sequences involved in gene regulation many biological processes and diseases. The lack of a complete comprehension their functionality, especially genome-wide scenario, has demanded new computational approaches to annotate roles. It is widely known that secondary structure determinant know RNA function machine learning based have been successfully proven predict from information. Here we show can be predicted with good accuracy raw...
Abstract Background:Glioblastoma multiforme (GBM) is a highly aggressive primary brain tumor refractory to standard treatments and immunotherapy with immune-checkpoint inhibitors (ICI) (PMID: 35626018). Interestingly, melanoma metastases (MM-BM), sharing the same niche as GBM, often respond current ICI immunotherapies 36521332). The role of epigenetic modifications in regulating GBM cellular proliferation, invasion, prognosis, well their impact on cross-talk between immune cells milieu, has...
Abstract Cell-free DNA (cf-DNA) circulates in the blood due to cell death, which can result from normal cellular processes or specific diseases such as cancer and others. The set of epigenetic footprints cf-DNA, nucleosome organization, end-motifs distribution, fragmentation pattern, methylation signatures, constitute a key factor non-tumor-informed liquid biopsies because status is highly tissue-specific distinguish types subtypes. We developed Fragment Analysis for Tumor Evaluation with...
Abstract Background co-targeting of immune checkpoint inhibitors (ICI) CTLA-4 and PD-1 has recently become the new first-line standard care therapy pleural mesothelioma (PM) patients, with a significant improvement overall survival over conventional chemotherapy. The analysis by tumor histotype demonstrated greater efficacy ICI in non-epithelioid (non-E) vs epithelioid (E) PM; although some E PM patients also benefit from treatment. This evidence suggests that molecular features, beyond...
Abstract Viral mimicry refers to the activation of innate anti-viral immune responses due induction endogenous retroelement (RE) expression. has been previously described augment anti-tumor and sensitize solid tumors immunotherapy including colorectal cancer, melanoma, clear renal cell carcinoma. Here, we found that targeting a novel, master epigenetic regulator, Zinc Finger Protein 638 (ZNF638), induces viral in glioblastoma (GBM) preclinical models potentiates checkpoint inhibition (ICI)....
Abstract Clinical trials using immune checkpoint inhibition(ICI) have traditionally failed in glioblastoma (GBM). Viral mimicry, which augments anti-tumor responses and sensitizes response to immunotherapy other cancers, involves the epigenetic activation of endogenous retroelements (REs). REs are silenced via HUSH complex H3K9me3. This process is mediated by ZNF638. We aimed elucidate role viral mimicry enhancing ICI through reprogramming complex. demonstrated that RE expression among 48...
Abstract Association of DNA hypomethylating agents (DHA) with immune-checkpoint inhibitors (ICI) is a promising strategy to improve efficacy ICI-based therapy. Here we report the five-year clinical outcome and an integrated multi-omics analysis pre- on-treatment lesions from advanced melanoma patients enrolled in phase Ib NIBIT-M4 study, dose-escalation trial DHA agent guadecitabine combined ipilimumab. With minimum follow-up 45 months median OS was 25.6 months; 5-year rate 28.9% DoR 20.6...