A5065893854- DNA Repair Mechanisms
- Genetic factors in colorectal cancer
- Computational Drug Discovery Methods
- SARS-CoV-2 and COVID-19 Research
- vaccines and immunoinformatics approaches
- PARP inhibition in cancer therapy
- Cancer-related Molecular Pathways
- Cancer Genomics and Diagnostics
- Epigenetics and DNA Methylation
- Microtubule and mitosis dynamics
- CRISPR and Genetic Engineering
- Health, Environment, Cognitive Aging
- Genomics and Chromatin Dynamics
- Science, Research, and Medicine
- Pluripotent Stem Cells Research
- Adipose Tissue and Metabolism
- Cancer, Hypoxia, and Metabolism
- Cancer Cells and Metastasis
- Nuclear Receptors and Signaling
- Tissue Engineering and Regenerative Medicine
- Integrated Circuits and Semiconductor Failure Analysis
- Pancreatic and Hepatic Oncology Research
- Bacteriophages and microbial interactions
- Mitochondrial Function and Pathology
- Prostate Cancer Treatment and Research
University of Geneva
2017-2025
NBE Therapeutics (Switzerland)
2024
University Hospital of Geneva
2023
Biomedical Research Foundation of the Academy of Athens
2017-2021
National and Kapodistrian University of Athens
2020
Abstract An important advance in cancer therapy has been the development of poly(ADP-ribose) polymerase (PARP) inhibitors for treatment homologous recombination (HR)-deficient cancers 1–6 . PARP trap PARPs on DNA. The trapped are thought to block replisome progression, leading formation DNA double-strand breaks that require HR repair 7 Here we show PARP1 functions together with TIMELESS and TIPIN protect early S phase from transcription–replication conflicts. Furthermore, synthetic lethality...
Mpro, the main protease of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is essential for viral life cycle. Accordingly, several groups have performed in silico screens to identify Mpro inhibitors that might be used treat SARS-CoV-2 infections. We selected more than five hundred compounds from top-ranking hits two very large on-demand synthesis. then examined whether these could bind and inhibit its activity. Two interesting chemotypes were identified, which further evaluated...
Aberrant replication causes cells lacking BRCA2 to enter mitosis with under-replicated DNA, which activates a repair mechanism known as mitotic DNA synthesis (MiDAS). Here, we identify genome-wide the sites where MiDAS reactions occur when is abrogated. High-resolution profiling revealed that these are different from at aphidicolin-induced common fragile in they map genomic regions replicating early S-phase, close early-firing origins, highly transcribed, and display R-loop-forming...
Given the clinical, economic, and societal impact of obesity, unraveling mechanisms adipose tissue expansion remains fundamental significance. We previously showed that white (WAT) levels 3-mercaptopyruvate sulfurtransferase (MPST), a mitochondrial cysteine-catabolizing enzyme yields pyruvate sulfide species, are downregulated in obesity. Here, we report Mpst deletion results fat accumulation mice fed high-fat diet (HFD) through transcriptional metabolic maladaptation. Mpst-deficient on HFD...
DNA replication initiates at genomic loci known as origins, which fire according to a spatiotemporal program, still not yet well-defined in mammals. Here, we investigated whether pluripotent mouse embryonic stem cells (mESCs), proliferate rapidly and have very short G1 phases, different origin firing program than differentiated cells. Using EdU-seq combined with various cell cycle synchronization methods, identified initiation zones (IZs) mESCs, mesenchymal embryo fibroblasts (MEFs). Similar...
Abstract Background MASLD is an increasing health global problem characterized by the accumulation of liver-fat. patients can progress to MASH, a more severe stage disease liver inflammation and oxidative stress background. These two hallmarks are believed drive HCC formation, although molecular mechanisms not well understood. Aims Characterize that oxidation backgrounds in MASH livers cause formation. Methods MC4R KO mice were fed with chow or western diet harvested at 33-38 weeks develop...
Abstract Chromatin licensing and DNA replication factor 1 (CDT1), a protein of the pre‐replicative complex, is essential for loading minichromosome maintenance complex (MCM) helicases onto origins replication. While several studies have shown that dysregulation CDT1 expression causes re‐replication damage in cell lines, highly expressed human cancers, whether deregulation sufficient to enhance tumorigenesis vivo currently unclear. To delineate its role , we overexpressed Cdt1 mouse colon...
The most prevalent single-nucleotide substitution (SNS) found in cancers is a C-to-T the CpG motif. It has been proposed that many of these SNSs arise during organismal aging, prior to transformation normal cell into precancerous/cancer cell. Here, we isolated single intestinal crypts derived from tissue or adenomas Apcmin/+ mice, expanded them minimally vitro as organoids, and performed exome sequencing identify point mutations had acquired vivo at single-cell level. SNSs, being CpG-to-TpG...
The analysis of bacterial genomes is a potent tool to investigate the distribution specific traits related ability surviving in particular environments. Among associated with adaptation hostile conditions, toxin–antitoxin (TA) systems have recently gained attention lactic acid bacteria. In this work, genome sequences Lacticaseibacillus strains dairy origin were compared, focusing on type I TA homologous Lpt/RNAII and most common II systems. A high number been identified spread all analyzed...
The Notch signaling pathway mediates cell-cell communication regulating cell differentiation and proliferation fate decisions in various tissues. In the urinary bladder, acts as a tumor suppressor mice, while mutations components have been identified human bladder cancer well. Here we report that genetic inactivation of mice leads to downregulation cell-ECM interaction components, including proteins previously implicated interstitial cystitis/bladder pain syndrome (IC/BPS), structural...
The genomes of many human CRCs have been sequenced, revealing a large number genetic alterations. However, the molecular mechanisms underlying accumulation these alterations are still being debated. In this study, we examined colorectal tumours that developed in mice with Apclox/lox, LSL-KrasG12D, and Tp53lox/lox targetable alleles. Organoids were derived from single cells spectrum mutations was determined by exome sequencing. nucleotide substitutions (SNSs) correlated age tumour, but...
ABSTRACT M pro , also known as 3CL is the main protease of SARS-CoV-2 coronavirus and, such, essential for viral life cycle. Two studies have each screened and ranked in silico more than one billion chemical compounds an effort to identify putative inhibitors . More five hundred seven thousand top-ranking hits were synthesized by external supplier examined with respect their activity two biochemical assays: a assay thermal shift assay. clusters inhibitory identified. An additional molecules,...
Abstract The formation of poly(ADP-ribose) (PAR) chains from NAD+ precursors by PARP enzymes is a characteristic posttranslational modification during DNA damage repair. PAR function as docking platforms for repair proteins that are required to resolve lesions. Equally important the subsequent removal protein substrates conclude process and restore genomic integrity. Poly(ADP-ribose) glycohydrolase (PARG) key enzyme in this has recently garnered significant attention novel cancer target....
Abstract An important advance in cancer therapy the last decade has been development of poly ADP-ribose polymerase (PARP) inhibitors for treatment select ovarian and breast cancers. The clinical benefit stems from synthetic lethality PARP with homologous recombination (HR) deficiency, which deficiency is prevalent types listed above. current model to explain based on observation that trap PARPs DNA: trapped block progression replisome, leading formation DNA double-strand breaks (DSBs),...
Abstract Background The maintenance of genome stability is a key process to slow aging. One the mechanisms ensuring this correct coordination origins replication (ORI), resulting in successful transmission DNA. Previously, we mapped and compared ORI firing between young aged mice vivo, using regenerating liver mouse model. We confirmed decreased hepatocyte efficiency mice, known have impaired regeneration. proved be fully rescued when blocking mice's ATR serine/threonine-protein kinase,...