Understanding how low UPF1 expression leads to drug resistance in bladder cancers

About the Project

Currently, standard of care for muscle invasive bladder cancer after surgery involves radiation and platinum therapy in combination with other DNA damage-inducing agents and replication inhibitors [8].

Whilst initial response rates to these drugs are fairly high (36-65%), this response does not translate to overall survival (15% at 5 year overall survival) suggesting that chemo-resistance appears in almost all tumours as disease progresses [7, 9]. How and why this occurs is largely unknown and means by which to treat these patients are urgently needed.

We have discovered that low expression levels of a specific protein, often down-regulated in bladder cancers, leads to an impaired response to replication stress and DNA damage and consequently, resistance to standard drugs such as cisplatin and radiotherapy.

This project will 1. Assess levels of this protein in biobanked bladder cancer tissue samples and correlate with stored patient data. 2. Access patient bladder cancer samples direct from surgery and assess protein and RNA levels along with response to a panel of drugs. 3. Uncover the mechanism behind this resistance in order to develop new anti-cancer drugs.

This is an exciting opportunity to work with both clinicians and research scientists to improve cancer treatment for bladder cancer patients.

Proposed start date: 01 October 2026

Entry Requirements:

Candidates must have a first or upper second class honours degree with significant research experience.

How to apply:

Please complete a University Postgraduate Research Application form available here: http://www.shef.ac.uk/postgraduate/research/apply

Please clearly state the prospective main supervisor in the respective box and select School of Clinical Medicine as the department.

Enquiries:

Interested candidates should in the first instance contact Dr Ruth Thompson (R.H.Thompson@Sheffield.ac.uk).

Funding Notes

Open to UK and Overseas self funded students.

This project does not have funding associated and applicants will need to find their own funding.

In addition to tuition fees, a fee of £15,000 per annum will be charged for project costs.