Assessing the role of PFKFB3 on regulating the tumour immune microenvironment and therapy response in hepatocellular carcinoma.

About the Project

Are you interested in investigating the mechanistic basis of metabolic reprogramming in liver cancer to help find new therapeutic opportunities?

Hepatocellular cancer (HCC) is the primary cause of liver cancer and is now the is the 3rd leading cause of cancer-related mortality worldwide and has an ~18% five-year survival rate due to late diagnosis. The current gold standard treatment for advanced HCC is immunotherapy, however, for many patients, this is unsuccessful, due to an immunosuppressive tumour immune-microenvironment (TIME).  Therefore, novel systemic therapies are needed to treat advanced HCC.

PFKFB3 is a key glycolytic enzyme that when expressed can strongly induce glycolysis, and has been shown to metabolically reprogram hepatocytes, macrophages and fibroblasts in the diseased liver, and high-PFKFB3 levels correlate with reduced HCC patient survival.

This PhD will use pre-clinical mouse models and complex 3D cell cultures (including ex vivo precision cut liver or tumour slice cultures) of HCC, to explore the impact of cell-specific modulation of PFKFB3, to interrogate the disease HCC biology and identify new drug targets.  Novel therapeutic approaches will be tested in PCTS and patient derived HCC cell lines. The student will be fully trained in preclinical mouse models, advanced histological and molecular (flow and scRNA-seq) methods.

The student will be embedded into the Newcastle fibrosis research groups and have access to a wide range of mentorship.

Funding

Students who have, or are expecting to attain, at least an upper second-class honours degree (or equivalent) in a relevant subject, are invited to apply. Funding is available for Home (UK) students to cover tuition fees, a tax-free stipend at the UKRI rate (indicative amount in year 1 in 2026-27, £21,805) and research costs, for four years. Applicants normally required to cover International fees will have to cover the difference between the Home and the International tuition fee rates. There is no additional funding available to cover NHS Immigration Health Surcharge (IHS) costs, visa costs, flights etc.

Funding for this studentship is awarded on a competitive basis and is not guaranteed; availability will depend on the outcome of the selection process and subject to final approval by the University.