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The William Harvey Research Institute - Faculty of Medicine and Dentistry

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Investigating how epigenetic dysregulation modifies cell fate in oral cancer

Code: BC-DTP_2026_03

Title: Investigating how epigenetic dysregulation modifies cell fate in oral cancer

Primary Supervisor: Dr Adrian Biddle
Email: a.biddle@qmul.ac.uk 

Institute: Blizard Institute

Secondary Supervisor: Prof Helen Rowe
Email: h.rowe@qmul.ac.uk 

Institute: Blizard Institute

Lay Summary:

Oral squamous cell carcinoma (OSCC) is a common and increasingly prevalent cancer with persistently poor survival rates. A major challenge in OSCC is understanding why some tumours progress rapidly and metastasise, while others do not. Emerging evidence suggests that chronic inflammation plays a central role in driving tumour progression, yet the molecular mechanisms underlying this inflammatory state remain unclear.

This project focuses on a recently identified link between epigenetic dysregulation and cancer-associated inflammation. In healthy cells, the HUSH complex suppresses transposable elements, preventing their expression. In OSCC, we have observed downregulation of a key HUSH component (MPP8), accompanied by reactivation of LINE-1 transposable elements. Their activity produces nucleic acid fragments that trigger a sustained interferon response, a hallmark of chronic inflammation. Inflammation is known to promote tumour cell plasticity, particularly epithelial-mesenchymal transition (EMT) which is a key driver of invasion and metastasis. HUSH dysfunction may therefore represent a critical upstream event in OSCC progression.

The project will combine high-resolution analysis of human OSCC tissue with an advanced tumour-on-a-chip model that faithfully reconstructs the tumour microenvironment. Using multiplex imaging, genetic manipulation, and single-cell quantitative approaches, we will map how HUSH activity, transposable element activation, interferon signalling, and EMT interact across different stages of disease.

By defining this novel epigenetic–inflammatory axis, the study aims to uncover new biomarkers of OSCC progression and identify potential therapeutic targets. The work will provide a rich training environment in cancer biology, epigenetics, imaging, microfluidics, and data-driven single-cell analysis.

Aims and Objectives:

To address the hypothesis and build on initial observations in other cancer models and in patient tissue we aim to:

  1. Explore the regulation of HUSH complex, histone modifications, retrotransposon activation and interferon responses in human OSCC tissue at different stages of progression, and correlate this with tumour EMT and TME changes.
  2. Determine the mechanism through which HUSH complex regulates key features of tumour progression in a tumour-on-a-chip model of OSCC invasion into a complex TME.

References:

  • Mauceri R, et al. 2022. doi:10.3389/fpsyg.2022.1009080.
  • Duggan MA, et al. 2016. doi:10.1097/pas.0000000000000749.
  • Niklander SE. 2021. doi:10.3389/froh.2021.642238.
  • Tunbak H, et al. 2020. doi:10.1038/s41467-020-19170-5.
  • Robbez-Masson L, et al. 2018. doi:10.1101/gr.228171.117.
  • Tie CH, et al. 2017. doi:10.1016/j.coviro.2017.06.007.
  • Suarez-Carmona M, et al. 2017. doi:10.1002/1878-0261.12095.
  • Biddle A, et al. 2011. doi:0008-5472.CAN-11-1059 [pii] 10.1158/0008-5472.CAN-11-1059.
  • Youssef G, et al. 2023. doi:10.7554/eLife.90298.
  • Scemama A, et al. 2024. doi:10.1101/2024.01.02.573897.
  • Biddle A, et al. 2016. doi:10.1016/j.ebiom.2016.01.007.
  • Yu X, et al. 2024. doi:10.1038/s41420-024-01803-z.



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