Project description
Epigenetics in HPV-associated cancer
Human papillomavirus (HPV)-positive oropharyngeal cancer is a rapidly rising subtype of head and neck cancer, driven by HPV infection rather than tobacco or alcohol. While prognosis is generally favourable, a significant proportion of patients relapse or develop metastases, reflecting considerable variability in tumour behaviour that current tools cannot predict. With the support of the Marie Skłodowska-Curie Actions programme, the EPiTOME-M project will focus on the epigenetic mechanisms underlying this variability. Researchers will use single-cell DNA methylation profiling, patient-derived organoids and CRISPR-based tools to identify cell-type-specific epigenetic signatures. Moreover, they will map regulatory DNA structures and examine how telomere length influences immune responses within the tumour. Findings will enable novel biomarker discovery and improve patient stratification for personalised treatment.
Objective
HPV-positive oropharyngeal squamous cell carcinoma (HPV+ OPSCC) is a rapidly rising, clinically distinct subtype of head and neck cancer. Despite favourable prognosis, 1/3rd of patients relapse and 5–13% develop metastases within 3 years, reflecting marked interpatient and intra-tumoral heterogeneity and thus impacting treatment response. EPiTOME-M aims to address this challenge by identifying the cell of origin and dissecting epigenetic mechanisms driving heterogeneity and immune evasion. Current studies rely on bulk sequencing, which mask cell-type–specific signals and spatial complexity. I will apply sciMET-seq, a single-cell DNA methylation technology to create reference methylomes from normal tonsil and HPV+ OPSCC tissues, to identify lineage-specific epigenetic signatures. Building on this, I will map G-quadruplex (G4) structures—non-canonical DNA elements known to modulate methylation—within differentially methylated regions and test their functional impact using CRISPRi in HPV˖ OPSCC cell lines. Additionally, I will use patient-derived organoids to examine how telomere length influences the tumour immune microenvironment. This multidisciplinary approach—combining epigenomics, telomere biology, and immunology—will yield mechanistic insights into tumour heterogeneity and immune modulation, enabling novel biomarker discovery and precision stratification in HPV˖ OPSCC. The project will foster a two-way knowledge exchange between me and the host institutions, RCSI and secondment host KU Leuven. This includes expertise in DNA methylation and biomarker development, clinical insight and sample access (RCSI), telomere biology expertise (my contribution), and training in single-cell genomics (KU Leuven). Ultimately, by integrating these strengths, the fellowship will empower me to address a critical question in HPV+ OPSCC and establish a strong, independent research profile at the interface of telomere biology, epigenomics, and oncology.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences genetics DNA
- medical and health sciences clinical medicine oncology
- medical and health sciences health sciences infectious diseases viral diseases DNA viruses
- natural sciences biological sciences genetics epigenetics
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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(opens in new window) HORIZON-MSCA-2025-PF
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
D02 YN77 DUBLIN 2
Ireland
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