Inhibiting the S6 kinase 2/hnRNPA1 pathway to sensitise osteosarcoma to CAR T-cell therapy

About the Project

An opportunity has arisen for a 4-year PhD studentship within the Department of Surgery and Cancer at Imperial College London funded by Sarcoma UK.

Osteosarcoma, the principal bone cancer, has so far proven resistant to the immunotherapeutic approaches that have revolutionised the treatment of other solid tumour types.

We found that targeting the RNA-binding protein hnRNPA1 or its upstream activating kinase, S6K2, leads to sensitisation of osteosarcoma cells to interferon gamma (IFNγ) and tumour necrosis factor alpha (TNFα), two of the principal mediators of the anticancer immune response. In addition, it increases the nuclear export of mRNA encoding for pro-immunogenic cytokines and various antigen presenting molecules involved in stimulating the activity of natural killer (NK) cells and cytotoxic T lymphocytes (CTLs).

This project will investigate how inhibition of the S6K2/hnRNPA1 axis promotes adoptive T-cell therapy with chimeric antigen receptors (CAR) T-cells recognising universal targets present on solid tumours, including osteosarcoma cells. It will define the repertoire of pro-immunogenic cytokines and surface molecules expressed by osteosarcoma cells following inhibition of this signalling axis. It will then reveal how this modulates the response to our existing CAR T-cell panel using advanced in vitro 2D/3D models and patient-derived organoids. Finally, it will test in a metastatic osteosarcoma mouse model the efficiency of the best performing combination between S6K2/hnRNPA1 inhibition and a particular CAR T-cell in clearing established tumours.

This project will be run in collaboration with Dr Sebastien Wälchli (University of Oslo, Norway).

Tuition fees are covered by the studentship for applicants who are UK nationals or have permanent leave to remain in the UK. Overseas applicant may apply, but with the understanding that they will be required to self-fund the additional fees (~£39,000 per year for 3.5 years). Applicants should hold or expect to obtain a first or upper-second class honours degree or equivalent in Cell Biology, Molecular Biology or Biochemistry. A Master’s degree in one of the above fields is expected.

The annual stipend will be £22,780.00 tax-free.

Applicants should submit their CV and a covering letter, including full contact details of two referees, to Dr Olivier E Pardo (o.pardo@imperial.ac.uk). Imperial College PhD entry requirements must be met and the successful applicant will subsequently need to apply online. For further information please contact Dr Olivier E Pardo (o.pardo@imperial.ac.uk, tel: 07946914196).

Closing date: 10/06/2026

Funding Notes

Fees are fully funded for UK students and students with right to remain in the UK. Overseas applicants may apply if they are able to cover the difference in cost between UK fees and international student fees which is ~£39,000 per year for 3.5 years.