Project description:Therapy-related acute myeloid leukaemia (t-AML) is a late adverse effect of previous chemotherapy(ct-AML) and/or radiotherapy (rt-AML) or immunosuppressive treatment. t-AMLs represent ~10-20% of all AML cases, are extremely aggressive and have a poor prognosis in comparison to de novo AML. We hypothesised that in rt-AML, exposure to radiation leads to genome-wide epigenetic modifications. An epigenome-wide association study was conducted, measuring over 850K methylation sites across the whole genome in 14 donors. We focused on 94K sites lying in CpG-rich gene promoter regions. Overall, we found genome-wide hypo-methylation in AML and identified specific genes with promoter hyper-methylation. Additionally, pyrosequencing was used to quantify the methylation in 24 samples. We confirmed that the promoters of the genes MEST and GATA5, both previously reported as tumour suppressors, were specifically hyper-methylated in rt-AML in comparison to control and other subtypes of t-AML. These may represent the epigenetic contribution to rt-AML development at the molecular level and be potential drug targets in rt-AML.
Project description:gDNA from patient samples with multiple basal cell carcinomas and possible exposure to ionizing radiation was hybridized Vs. GM12878 gDNA to assess CNAs. We aimed to find a possible common aberration pattern related to ionizing radiation or a rare metastasis.
Project description:Tardigrades can survive remarkable doses of ionizing radiation, up to about 1000 times the lethal dose for humans. How they do so is incompletely understood. We found that the tardigrade Hypsibius exemplaris suffers DNA damage upon gamma irradiation, but damage is repaired. We show that tardigrades have a specific and robust response to ionizing radiation: irradiation induces a rapid, dramatic upregulation of many DNA repair genes. By expressing tardigrade genes in bacteria, we validate that increased expression of some repair genes can suffice to increase radiation tolerance. We show that at least one such gene is necessary for tardigrade radiation tolerance. Tardigrades’ ability to sense ionizing radiation and massively upregulate specific DNA repair pathway genes may represent an evolved solution for maintaining DNA integrity.
Project description:Lycopene, a carotenoid known for its potent anti-inflammatory, antioxidant, and immune-modulating properties, is widely utilized in food, nutraceuticals, and medicine. This study aimed to explore the protective and therapeutic effects of lycopene against ionizing radiation-induced intestinal injury. Using a C57BL/6 mouse model exposed to ionizing radiation, we assessed the protective effects of lycopene by analyzing intestinal histology and serological markers. Our findings reveal that ionizing radiation induces oxidative stress, inflammation, and apoptosis in the intestinal epithelium. Lycopene administration effectively mitigated these effects by reducing oxidative stress, decreasing inflammatory responses, and inhibiting apoptosis. Mechanistically, lycopene was found to regulate key metabolic pathways, including linoleic acid and arachidonic acid metabolism, thereby exerting its anti-inflammatory and immune-modulatory effects. These results highlight lycopene's potential as a therapeutic agent for managing radiation-induced intestinal injury, offering a promising strategy for improving the clinical outcomes of patients undergoing radiotherapy.
Project description:The goal of the study is to identify differentially expressed isoforms in response to SRSF1 knockdown and/or ionizing radiation in HEK293T cells
Project description:Genome-wide expression analysis comparison with and without ionizing radiation in p53 mutant and wild type Drosophila larvae Genome-wide expression analysis comparison with and without ionizing radiation in p53 mutant (p53^5A-1-4) and wild type (y^1 w^1118) Drosophila third instar larvae. 4000R of X-rays used in IR-treated Drosophila. Analyzed 2hr and 18hr after exposure with age-matched larvae in non-treated controls.
Project description:This project explored the relationship between ionizing radiation and antigen presentation using both proteomic and immunopeptidomics methodologies. We investigated the radiation-specific changes which occur in the colorectal tumor cell proteome associated with changes in dose and time after irradiation. We used this data to observe the changes in key regulators and effector proteins of the antigen processing and presentation machinery. Furthermore, a parallel immunopeptidomics analysis enabled a peptide-level assessment of antigen presentation to correlate changes observed in the proteome thereby defining a radiation-specific peptide repertoire. A nuanced relationship between protein expression and antigen presentation was observed where radiation-induced changes in proteins do not always correlate with increased presentation of associated peptides. Furthermore, a neoantigen which increases in the context of radiation was characterised. This study provides new insights into how radiation enhances antigen processing and presentation that could be suitable for the development of combinatorial therapies.