Overview
Cholangiocarcinoma, or bile duct cancer, is one of the most challenging cancers to treat, with fewer than 10% of patients surviving five years after diagnosis. Its resistance to treatment stems from a highly immunosuppressive tumour microenvironment that disables immune cells, even advanced immunotherapies such as CAR-T and CAR-NK cells. These immune cells fail in the tumour’s nutrient-poor, oxygen-depleted conditions. To address this, new approaches are needed to re-energise immune cells and weaken tumour defences.
About this opportunity
This project explores a new direction in cancer therapy: manipulating metabolism to reshape the tumour microenvironment and enhance immune cell function within and outside the tumour environment. The focus is on mitochondrial uncouplers—agents that modulate energy production to alter cellular metabolism. Several of these, including niclosamide, are already licensed for other uses and have shown strong potential to influence immune and tumour cell activity. The project will assess how niclosamide can reprogramme the metabolic and functional aspects of both cancer and immune cells, improving the effectiveness of cell-based immunotherapies.
You will work at the intersection of immunology, metabolism, and cancer biology, using patient-derived 3D liver tumour models and precision-cut tumour slice cultures to recreate the tumour environment ex vivo. These systems will be used to test mitochondrial uncouplers alongside immune cell therapies to determine how metabolic reprogramming affects immune activity and tumour killing.
During the studentship, you will gain advanced training in a suite of immunological and analytical techniques to characterise how metabolic modulation influences immune–tumour interactions. This includes high-content flow cytometry to define immune-cell phenotypes, activation markers, and exhaustion states; multiplex cytokine and chemokine assays to map immune signalling; and ELISpot, intracellular cytokine staining, and cell cytotoxicity assays to assess T-cell and NK-cell function. You will also apply high-content imaging and metabolomic profiling to track changes in energy use, mitochondrial activity, and redox balance within tumour and immune cells. These methods will be combined with 3D co-culture models and patient-derived tissue systems to deliver physiologically relevant insights. Through this integrated approach, you will determine how mitochondrial uncouplers reshape immune metabolism, reverse tumour-induced suppression, and enhance cell therapies.
Benefits of being in the DiMeN DTP:
This project is part of the Discovery Medicine North Doctoral Training Partnership (DiMeN DTP), a diverse community of PhD students across the North of England researching the major health problems facing the world today. Our partner institutions (Universities of Leeds, Liverpool, Newcastle, York and Sheffield) are internationally recognised as centres of research excellence and can offer you access to state-of-the-art facilities to deliver high impact research.
We are very proud of our student-centred ethos and committed to supporting you throughout your PhD. As part of the DTP, we offer bespoke training in key skills sought after in early career researchers, as well as opportunities to broaden your career horizons in a range of non-academic sectors.
Being funded by the MRC means you can access additional funding for research placements, training opportunities or internships in science policy, science communication and beyond.
Further information on the programme and instructions on how to apply, including a link to the application portal, can be found on our website https://www.dimen.org.uk/