A5003537036- Genetics and Neurodevelopmental Disorders
- Genomics and Chromatin Dynamics
- CRISPR and Genetic Engineering
- Parkinson's Disease Mechanisms and Treatments
- Epigenetics and DNA Methylation
- Metabolomics and Mass Spectrometry Studies
- Autophagy in Disease and Therapy
- Nerve injury and regeneration
- Neuroinflammation and Neurodegeneration Mechanisms
- Chromosomal and Genetic Variations
- Endoplasmic Reticulum Stress and Disease
- Neurogenesis and neuroplasticity mechanisms
- Mitochondrial Function and Pathology
- Bioinformatics and Genomic Networks
- Cancer Genomics and Diagnostics
- Plant-Microbe Interactions and Immunity
- Gene Regulatory Network Analysis
- Cellular transport and secretion
- Diffusion and Search Dynamics
- Glioma Diagnosis and Treatment
- Metabolism and Genetic Disorders
- Genomics and Rare Diseases
- Peptidase Inhibition and Analysis
- Molecular Communication and Nanonetworks
- Immune cells in cancer
Vita-Salute San Raffaele University
2021-2024
Istituti di Ricovero e Cura a Carattere Scientifico
2021-2024
Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele
2021-2024
San Raffaele University of Rome
2022-2023
Institute of Biomedical Technologies
2018
National Research Council
2018
Abstract Recent findings in human samples and animal models support the involvement of inflammation development Parkinson’s disease. Nevertheless, it is currently unknown whether microglial activation constitutes a primary event neurodegeneration. We generated new mouse model by lentiviral-mediated selective α-synuclein (αSYN) accumulation cells. Surprisingly, these mice developed progressive degeneration dopaminergic (DA) neurons without endogenous αSYN aggregation. Transcriptomics...
Neuroinflammation plays a key role in exacerbating dopaminergic neuron (DAN) loss Parkinson’s disease (PD). However, it remains unresolved how to effectively normalize this immune response given the complex interplay between innate and adaptive responses occurring within scarcely accessible organ like brain. In study, we uncovered consistent correlation neuroinflammation, brain parenchymal lymphocytes, DAN among several commonly used mouse models of PD generated by variety pathological...
Abstract The investigation of genetic forms juvenile neurodegeneration could shed light on the causative mechanisms neuronal loss. Schinzel-Giedion syndrome (SGS) is a fatal developmental caused by mutations in SETBP1 gene, inducing accumulation its protein product. SGS features multi-organ involvement with severe intellectual and physical deficits due, at least part, to early neurodegeneration. Here we introduce human model that displays disease-relevant phenotypes. We show neural...
Wolfram syndrome 1 (WS1) is a rare genetic disorder caused by mutations in the WFS1 gene leading to wide spectrum of clinical dysfunctions, among which blindness, diabetes, and neurological deficits are most prominent. encodes for endoplasmic reticulum (ER) resident transmembrane protein wolframin with multiple functions ER processes. However, -dependent etiopathology retinal cells unknown. Herein, we showed that Wfs1 mutant mice developed early electrophysiological impairments followed...
Abstract Within the chromatin, distal elements interact with promoters to regulate specific transcriptional programs. Histone acetylation, interfering net charges of nucleosomes, is a key player in this regulation. Here, we report that oncoprotein SET critical determinant for levels histone acetylation within enhancers. We disclose condition which accumulated, severe Schinzel-Giedion Syndrome (SGS), characterized by failure usage regulatory regions typically employed during fate commitment....
<title>Abstract</title> Breast cancer progression is driven by dynamic changes in tissue mechanics that promote phase transitions toward collective cell movement, immune activation, and invasion. While previous investigations primarily employed model systems of genetically identical cells, breast carcinoma consists heterogeneous populations varying genetic mechanical traits. The complex interplay between this diversity dynamics, affecting tumor progression, remains largely unexplored. Here,...
The investigation of plant organisms by means data-derived systems biology approaches based on network modeling is mainly characterized genomic data, while the potential proteomics largely unexplored. This delay caused paucity genomic/proteomic sequences and annotations which are fundamental to perform mass-spectrometry (MS) data interpretation. However, Next Generation Sequencing (NGS) techniques contributing filling this gap an increasing number studies focusing proteome profiling...
Current therapies remain unsatisfactory in preventing the recurrence of glioblastoma multiforme (GBM), which leads to poor patient survival. By rational engineering transcription factor SOX2, a key promoter GBM malignancy, together with Kruppel-associated box and DNA methyltransferase3A/L catalytic domains, we generated synthetic repressor named SOX2 epigenetic silencer (SES), induces transcriptional silencing its original targets. doing so, SES kills both glioma cell lines patient-derived...
TBL1XR1 gene is associated with multiple developmental disorders presenting several neurological aspects. The relative protein involved in the modulation of important cellular pathways and master regulators transcriptional output, including nuclear receptor repressors, Wnt signaling, MECP2 protein. However, mutations (including complete loss its functions) have not been experimentally studied a context, leaving knowledge gap mechanisms at basis diseases. Here, we show that Tbl1xr1 knock-out...
Pancreatic cancer (PC) has a very low survival rate mainly due to late diagnosis and refractoriness therapies. The latter also cause adverse effects negatively affecting the patients' quality of life, often requiring dose reduction or discontinuation scheduled treatments, compromising chances cure. We explored specific probiotic blend on PC mice xenografted with KRAS wild-type KRASG12D mutated cell lines alone together gemcitabine+nab-paclitaxel treatment then assess tumor volume clinical...
Abstract Alterations in the dopamine catabolic pathway are known to contribute degeneration of nigrostriatal neurons Parkinson’s disease (PD). The progressive cellular buildup highly reactive intermediate 3,4-dihydroxyphenylacetaldehye (DOPAL) generates protein cross-linking, oligomerization PD-linked αSynuclein (αSyn) and imbalance quality control. In this scenario, autophagic cargo sequestome-1 (SQSTM1/p62) emerges as a target DOPAL-dependent accumulation cytosolic clusters. Although...
Abstract Background Neurodevelopmental disorders (NDDs) are heterogeneous conditions due to alterations of a variety molecular mechanisms and cell dysfunctions. SETD5 haploinsufficiency leads NDDs chromatin defects. Epigenetic basis has been reported in an increasing number cases while mitochondrial dysfunctions more common within NDD patients than the general population. Methods We investigated vitro neural stem cells as well brain Setd5 mouse model interrogating its transcriptome,...
Short Structured Abstract Untargeted metabolomics by mass spectrometry technologies generates huge numbers of metabolite signals, requiring computational analyses for post-acquisition processing and databases identification. Web-based data solutions frequently include only a part the entire workflow thus use different platforms. The R package “margheRita” enhances fragment matching accuracy addresses complete metabolomic profiling in untargeted studies based on liquid chromatography (LC)...
Summary Wolfram syndrome 1 (WS1) is a rare genetic disorder caused by mutations in the WFS1 gene leading to wide spectrum of clinical dysfunctions, among which blindness, diabetes and neurological deficits are most prominent. encodes for endoplasmic reticulum (ER) resident transmembrane protein Wolframin with multiple functions ER processes. However, -dependent etiopathology retinal cells unknown. Herein, we showed that Wfs1 mutant mice developed early electrophysiological impairments...
SUMMARY Within the chromatin, distal elements interact with promoters to regulate specific transcriptional programs. Histone acetylation, interfering net charges of nucleosomes, is a key player in this regulation. Here, we report that onco-protein SET critical determinant for levels histone acetylation within enhancers. We disclose conditions which accumulated, including severe Schinzel-Giedion Syndrome (SGS), are characterized by failure usage regulatory regions typically employed during...