Uncovering The Role of R-loop-mediated Epigenetic Regulation in The Response to Anticancer Therapies
il y a 6 jours
**Uncovering the role of R-loop-mediated epigenetic regulation in the response to anticancer therapies**:
- Réf **ABG-132306**
- Sujet de Thèse
- 30/05/2025
- Financement public/privé
- Centre de la recherche en cancérologie de Toulouse (CRCT)
- Lieu de travail- Toulouse - Occitanie - France
- Intitulé du sujet- Uncovering the role of R-loop-mediated epigenetic regulation in the response to anticancer therapies
- Champs scientifiques- Biologie
- Santé, médecine humaine, vétérinaire
- Mots clés- R-loops, Transcription, Chromatin, Epigenetics, Cancer
**Description du sujet**:
- R-loops are unusual nucleic acid structures consisting of an RNA/DNA hybrid and a single stranded DNA (ssDNA). They form during transcription and regulate key physiological processes, including gene expression. However, R-loop imbalance, caused by their unscheduled formation or failure to be timely resolved, can lead to genome instability and deregulated gene expression and has been involved in oncogenesis and cancer progression. R-loop imbalance is emerging as a common feature of cancer cells, including oncogene-driven cancers. However, **R-loop role in the response to anticancer therapies remains poorly understood**.
Our project aims to **investigate the role of R-loops in driving transcriptional and epigenetic reprogramming in response to anticancer therapies**. For this, we will identify the transcriptional and epigenetic changes depending on R-loops in response to anticancer treatment, the molecular mechanisms through which R-loops trigger these changes and how they translate into phenotypic plasticity at the single-cell level and genome-wide. Addressing these questions will advance our mechanistic understanding of the response to anticancer treatments paving the way for the development of therapeutic strategies aimed at improving the efficiency of anticancer therapies.
- 3 Selected Publications _(PhD and Master students are underlined)
**1)**Geraud M*, Cristini A*, Salimbeni S*, Bery N, Jouffret V, Russo M, Ajello AC, Fernandez Martinez L, ( ) Capranico G#, Sordet O#. TDP1 mutation causing SCAN1 neurodegenerative syndrome hampers the repair of transcriptional DNA double-strand breaks. **_Cell Rep. 2024_** May 16;43(5):114214. _*Co-first authors_.
**2)** McCann JL*, Cristini A*, ( ) Miller KM#, Gromak N# and Harris RS#. APOBEC3B regulates R-loops and promotes transcription-associated mutagenesis in cancer. **_Nat Genet. 2023 _**Oct;55(10):1721-1734. _*Co-first authors_.
**3)** Cristini A, Tellier A, Constantinescu F, Accalai C, Albulescu LO, Heiringhoff R, ( ) Gromak N. RNase H2, mutated in Aicardi-Goutières syndrome, resolves co-transcriptional R-loops to prevent DNA breaks and inflammation. **_Nat Commun_**_. 2022_** May 26;13(1):2961.
**Main Techniques**:We will employ a wide range of techniques, including cell culture, high-content and confocal imaging, live imaging, cell culture, CRISPR-Cas9, NGS (such as DRIP-seq, RNA-seq, ChIP-seq).
**Prise de fonction**:
- 01/10/2025
**Nature du financement**:
- Financement public/privé
**Précisions sur le financement**:
- ANR
**Présentation établissement et labo d'accueil**:
- Centre de la recherche en cancérologie de Toulouse (CRCT)
**Site web**:
**Etablissement délivrant le doctorat**:
- Université de Toulouse- 20/07/2025
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