A5087867777- RNA modifications and cancer
- Genomics and Rare Diseases
- Cancer-related molecular mechanisms research
- Bioinformatics and Genomic Networks
- MicroRNA in disease regulation
- Epigenetics and DNA Methylation
- CRISPR and Genetic Engineering
- Genetics, Aging, and Longevity in Model Organisms
- Mitochondrial Function and Pathology
- Metabolism and Genetic Disorders
- Cholinesterase and Neurodegenerative Diseases
- Pluripotent Stem Cells Research
- RNA and protein synthesis mechanisms
- Protein Structure and Dynamics
- Sirtuins and Resveratrol in Medicine
- Microbial Metabolic Engineering and Bioproduction
- Tea Polyphenols and Effects
- Renal and related cancers
- Peptidase Inhibition and Analysis
- Adipose Tissue and Metabolism
- Genomics and Phylogenetic Studies
- Genetics and Neurodevelopmental Disorders
Sapienza University of Rome
2022-2024
Casa Sollievo della Sofferenza
2022-2024
Istituti di Ricovero e Cura a Carattere Scientifico
2022-2024
Abstract Mitochondrial dysfunction has pleiotropic effects and is frequently caused by mitochondrial DNA mutations. However, factors such as significant variability in clinical manifestations make interpreting the pathogenicity of variants genome challenging. Here, we present APOGEE 2, a mitochondrially-centered ensemble method designed to improve accuracy predictions for missense variants. Built on joint consensus recommendations American College Medical Genetics Genomics/Association...
The process of aging is a complex phenomenon that involves progressive decline in physiological functions required for survival and fertility. To better understand the mechanisms underlying this process, scientific community has utilized several tools. Among them, mitochondrial DNA emerged as crucial factor biological aging, given dysfunction thought to significantly contribute phenomenon. Additionally, Drosophila melanogaster proven be valuable model organism studying due its low cost,...
Abstract Background Obesity is a major health burden. Preadipocytes proliferate and differentiate in mature adipocytes the adipogenic process, which could be potential therapeutic approach for obesity. Deficiency of SIRT6, stress-responsive protein deacetylase mono-ADP ribosyltransferase enzyme, blocks adipogenesis. Mutants SIRT6 (N308K/A313S) were recently linked to long lifespan Ashkenazi Jews. In this study, we aimed clarify how these new centenarian-associated genetic variants affect...
KDM6A is the disease causative gene of type 2 Kabuki Syndrome, a rare multisystem disease; it also known cancer driver gene, with multiple somatic mutations found in few types. In this study, we looked at eleven missense variants lung squamous cell carcinoma, one most common subtypes, to see how they affect catalytic mechanisms. We that influence interaction histone H3 and exposure trimethylated Lys27, which critical for wild-type physiological function varying degrees, by altering...
Aim: Human induced pluripotent stem cells (iPSCs) are inefficiently derived from somatic by overexpression of defined transcription factors. Overexpression H2A histone variant macroH2A1.1, but not macroH2A1.2, leads to increased iPSC reprogramming unclear mechanisms. Materials & methods: Cleavage under targets and tagmentation (CUT&Tag) allows robust epigenomic profiling a low cell number. We performed an integrative CUT&Tag-RNA-Seq analysis macroH2A1-dependent orchestration iPSCs using...
Introduction Infantile hypotonia with psychomotor retardation and characteristic facies-1 (IHPRF1, MIM#615419) is a rare, birth onset, autosomal recessive disorder caused by homozygous or compound heterozygous truncating variants in NALCN gene (MIM#611549) resulting loss-of-function effect. Methods We enrolled new IHPRF1 patients’ cohort the framework of an international multicentric collaboration study. Using specialized silico pathogenicity predictors ad hoc structural analyses, we...
The recent identification of noncoding variants with pathogenic effects suggests that these variations could underlie a significant number undiagnosed cases. Several computational methods have been developed to predict the functional impact variants, but they exhibit only partial concordance and are not integrated annotation resources, making interpretation still challenging. MicroRNAs (miRNAs) small RNA molecules act as fine regulators gene expression play crucial functions in several...
Abstract The process of aging is a complex phenomenon that involves progressive decline in physiological functions required for survival and fertility. To better understand the mechanisms underlying this process, scientific community has utilized several tools. Among them, mitochondrial DNA emerged as crucial factor biological aging, given dysfunction thought to significantly contribute phenomenon. Additionally, Drosophila melanogaster proven be valuable model organism studying due its low...
ABSTRACT APOGEE 2 is a mitochondrially-centered ensemble method designed to improve the accuracy of pathogenicity predictions for interpreting missense mitochondrial variants. Built on joint consensus recommendations by American College Medical Genetics and Genomics/Association Molecular Pathology (ACMG/AMP), features an improved machine learning curated training set enhanced performance metrics. It offers region-wise assessments genome fragility mechanistic analyses specific amino acids...
ABSTRACT Human-induced pluripotent stem cells (iPSCs) can be derived from adult by forced expression of defined transcription factors. This paves the way for autologous iPSC-derived therapies, which, however, are not yet considered safe. Moreover, reprogramming somatic into iPSCs is an inefficient process, in range 0.1%–1%. The epigenetic mechanisms implicated well understood. substitution canonical histone H2A with macroH2A1 variant exon-spliced isoforms (macroH2A1.1 and macroH2A1.2)...