A5042421399- CAR-T cell therapy research
- DNA Repair Mechanisms
- Microtubule and mitosis dynamics
- RNA modifications and cancer
- Genomics and Chromatin Dynamics
- CRISPR and Genetic Engineering
- Photosynthetic Processes and Mechanisms
- Glioma Diagnosis and Treatment
- Carcinogens and Genotoxicity Assessment
- Neurogenetic and Muscular Disorders Research
- Immunodeficiency and Autoimmune Disorders
- Cancer, Hypoxia, and Metabolism
- Educational Robotics and Engineering
- Trace Elements in Health
- Semiconductor materials and devices
- DNA and Nucleic Acid Chemistry
- Zebrafish Biomedical Research Applications
- Axon Guidance and Neuronal Signaling
- Amyotrophic Lateral Sclerosis Research
- Neuroblastoma Research and Treatments
- Hippo pathway signaling and YAP/TAZ
- RNA Research and Splicing
- Autophagy in Disease and Therapy
- Plant Genetic and Mutation Studies
- Molecular Biology Techniques and Applications
Bambino Gesù Children's Hospital
2022-2024
University of Rome Tor Vergata
2023-2024
Istituto Superiore di Sanità
2016-2024
Departement Omgeving
2024
Abstract Stabilisation of stalled replication forks prevents excessive fork reversal and their pathological degradation, which can undermine genome integrity. Here we investigate a physiological role RAD52 at by using human cell models depleted RAD52, specific small-molecule inhibitor the RAD52-ssDNA interaction, in vitro single-molecule analyses. We demonstrate that degradation reversed MRE11. Mechanistically, binds to fork, promotes its occlusion counteracts loading SMARCAL1 vivo. Loss...
Abstract Purpose: Medulloblastoma (MB), the most common childhood malignant brain tumor, has a poor prognosis in about 30% of patients. The current standard care, which includes surgery, radiation, and chemotherapy, is often responsible for cognitive, neurologic, endocrine side effects. We investigated whether chimeric antigen receptor (CAR) T cells directed toward disialoganglioside GD2 can represent potentially more effective treatment with reduced long-term Experimental Design: expression...
Werner syndrome (WS) is a cancer-prone disease caused by deficiency of protein (WRN). WRN maintains genome integrity promoting replication-fork stability after various forms replication stress. Under mild stress, WS cells show impaired ATR-mediated CHK1 activation. However, it remains unclear if elicit other repair pathway. We demonstrate that loss leads to enhanced ATM phosphorylation upon prolonged exposure aphidicolin, specific inhibitor DNA polymerases, resulting in Moreover, we find...
Amyotrophic Lateral Sclerosis (ALS) is considered the prototype of motor neuron disease, characterized by loss and muscle waste. A well-established pathogenic hallmark ALS mitochondrial failure, leading to bioenergetic deficits. So far, pharmacological interventions for disease have proven ineffective. Trimetazidine (TMZ) described as a metabolic modulator acting on different cellular pathways. Its efficacy in enhancing muscular cardiovascular performance has been widely described, although...
R-loops are non-canonical DNA structures that form during transcription and play diverse roles in various physiological processes. Disruption of R-loop homeostasis can lead to genomic instability replication impairment, contributing several human diseases, including cancer. Although the molecular mechanisms protect cells against such events not fully understood, recent research has identified fork protection factors damage response proteins as regulators dynamics. In this study, we identify...
The MUS81 complex is crucial for preserving genome stability through the resolution of branched DNA intermediates in mitosis. However, untimely activation S-phase dangerous. Little known about regulation human and how deregulated affects chromosome integrity. Here, we show that CK2 kinase phosphorylates at Serine 87 late-G2/mitosis, upon mild replication stress. Phosphorylated interacts with SLX4, this association promotes function complex. In line a role mitosis, phosphorylation suppressed...
CS proteins have been involved in the repair of a wide variety DNA lesions. Here, we analyse role break by studying histone H2AX phosphorylation different cell cycle phases and comet assay CS-A CS-B primary transformed cells. Following methyl methane sulphate treatment significant accumulation unrepaired single strand breaks was detected cells as compared to normal cells, leading double S G2 phases. A delay DSBs were also observed following IR exposure. These data confirm CSB suppression...
Conflicts between replication and transcription are a common source of genomic instability, characteristic almost all human cancers. Aberrant R-loops can cause block to fork progression. A growing number factors involved in the resolution these harmful structures many perhaps still unknown. Here, we reveal that Werner interacting protein 1 (WRNIP1)-mediated response is implicated counteracting aberrant R-loop accumulation. Using cellular models with compromised Ataxia-Telangiectasia...
Medulloblastoma (MB) is the most common cerebellar malignancy during childhood. Among MB, MYC-amplified Group 3 tumors display worst prognosis. MYC an oncogenic transcription factor currently thought to be undruggable. Nevertheless, targeting MYC-dependent processes (i.e. and RNA processing regulation) represents a promising approach. We have tested sensitivity of MYC-driven MB cells pool splicing inhibitors that wide spectrum targets. them, we focus on THZ531, inhibitor transcriptional...
ABSTRACT Schimke immuno-osseous dysplasia is an autosomal recessive genetic osteochondrodysplasia characterized by dysmorphism, spondyloepiphyseal dysplasia, nephrotic syndrome and frequently T cell immunodeficiency. Several hypotheses have been proposed to explain the pathophysiology of disease; however, mechanism which SMARCAL1 mutations cause elusive. Here, we generated a conditional knockdown model in induced pluripotent stem cells (iPSCs) mimic conditions associated with severe form...
Failure to protect and/or restart stalled replication forks contributes genomic instability. Radiation-sensitive 51 (RAD51) recombinase defends from nucleolytic attack, which otherwise can threaten their integrity. Recently, we have uncovered a novel and key function of Werner helicase interacting protein 1 (WRNIP1) as fork-protective factor working in conjunction with RAD51 response stress.
R-loops are non-canonical DNA structures that form during transcription and play diverse roles in various physiological processes. Disruption of R-loop homeostasis can lead to genomic instability replication impairment, contributing several human diseases, including cancer. Although the molecular mechanisms protect cells against such events not fully understood, recent research has identified fork protection factors damage response proteins as regulators dynamics. In this study, we identify...
<p>Supplemental Figure 12. DAOY-GFP tumor bearing-mice treated with Tazemetostat to evaluate GD2 upregulation in vivo.</p>
<p>Supplemental Figure 5. Real-Time killing assay of CAR.GD2 T-cells vs DAOY-GFP cell line.</p>
<div>AbstractPurpose:<p>Medulloblastoma (MB), the most common childhood malignant brain tumor, has a poor prognosis in about 30% of patients. The current standard care, which includes surgery, radiation, and chemotherapy, is often responsible for cognitive, neurologic, endocrine side effects. We investigated whether chimeric antigen receptor (CAR) T cells directed toward disialoganglioside GD2 can represent potentially more effective treatment with reduced long-term...
<p>Supplemental Figure 6. CAR.GD2 T-cells spare the elimination of MB cells with a dim expression GD2.</p>
<p>Supplemental Figure 14. Orthotopic PDX mouse model of human MED-411 FH mCherry/Luc cell line to evaluate anti-tumor activity CAR.GD2 T-cells.</p>
<p>Supplemental Video 2. IncuCyte® live-cell System video of Cytotoxic activity NT or CAR.GD2 T-cells vs DAOY-GFP-FF-Luc cell line. The shows 84 hours tumor growth (DAOY line) with only (A) and cells co-cultured (B) (C).</p>