(Image: Dr James Nicholson, QMUL, Dr Nekisa Zakeri, QMUL, Dr Jayant Rane, UCLH, Prof Erik Sahai, Crick, Dr Rafael T. M. de Rosales, KCL, Dr Luigi Ombrato, QMUL)

A huge congratulations to all our Seed and Development Fund awardees, each receiving up to £25,000 to launch innovative pump-priming projects. Here is a insight to some of these projects;

Radiotherapy-induced epigenetic selection in glioblastoma recurrence

Glioblastoma is an aggressive brain tumour that almost invariably recurs after radiotherapy, yet shows surprisingly little evidence of genetic evolution during treatment. Dr Nicholson’s project tests a new model: that recurrence is driven not by genetic mutations, but by the selection of pre‑existing, heritable epigenetic cell states that are intrinsically resistant to radiation.

They will use single‑cell DNA methylation sequencing to profile thousands of tumour cells from matched primary and recurrent glioblastoma samples, alongside patient‑derived tumour models exposed to clinically relevant radiotherapy. This will identify rare epigenetic subpopulations present before treatment and track how they expand under therapeutic pressure. By integrating these data with spatial transcriptomics, the team will map where resistant cell states reside within the tumour microenvironment. Finally, they will test the clinical relevance of these signatures in a validation cohort of >1,000 bulk glioblastoma methylation profiles. Ultimately this project aims to inform the future development of rational combination therapies that target resistant populations and improve patient response to radiotherapy.

Radiotherapy-induced tumour priming to enhance gamma delta T cell immunotherapy for hepatocellular carcinoma

Hepatocellular carcinoma is a leading cause of cancer-related mortality worldwide, with limited effective therapeutic options for advanced disease. Dr Zakeri’s project investigates novel combination treatment approaches integrating radiation-induced tumour priming with gamma delta T cell immunotherapy for hepatocellular carcinoma. Using 3D patient-derived tumour models, the team will study the mechanisms by which radiotherapy impacts on tumour susceptibility to gamma delta T cell-mediated killing and remodels the tumour microenvironment.

Radiotherapy-induced regulatory T cell reprogramming and its impact on lung metastasis

Radiotherapy is one of the most powerful tools in cancer treatment, routinely used to control primary tumours. Yet its effects are not confined to the tumour itself: radiotherapy can reshape the immune system, with consequences across the body that remain unclear. Dr Ombrato’s project addresses a key unanswered question: how does radiotherapy to the breast influence the immune environment in distant organs such as the lung, a common site of metastatic disease? Using preclinical models, his team has identified systemic immune changes following treatment, including shifts in regulatory T cells (Tregs), which play a central role in controlling immune responses.

They will now investigate how these radiotherapy-induced immune alterations affect the behaviour of disseminated cancer cells in the lung. By uncovering the underlying biology, this work aims to inform the development of more effective treatment strategies that combine radiotherapy with immune-targeting approaches, ultimately helping to optimise cancer therapy in the context of metastatic disease.

Microenvironmental determinants of chemo-radiotherapy response in EOCRC

Colorectal cancer is increasingly being diagnosed in adults under 50, and some younger patients have poorer outcomes than expected despite being fit enough to receive intensive treatment. Dr Rane’s project asks whether the tissue surrounding these cancers helps explain this problem. Rather than studying cancer cells alone, they will recreate patient-derived tumour ecosystems in the laboratory, including cancer cells and key support and immune cells that can make tumours inflamed, scar-like and harder for treatment to penetrate. His team will use these models to study why early-onset bowel and rectal cancers may respond differently to chemotherapy and radiotherapy, including modern radiotherapy approaches. The aim is to generate evidence that helps doctors identify which patients need different treatment strategies, and to support future clinical trials designed to improve cure rates while preserving long-term quality of life for younger patients and families.

To read about our other Seed and Development fund projects click below;

Seed Funding
Development Funding