Differential Regulation of the Stimulator of Interferon Genes (STING) pathway in HPV+ and HPV- Head and Neck Cancer
Head and neck cancers (HNC) represent a heterogeneous cluster of aggressive, difficult to treat malignancies that account for 3% of cancers in the UK. Incidence of HNC in the UK and worldwide has increased by ~30% since 1990. 12,000 individuals were diagnosed with HNSCC in the UK in 2015, with the incidence in some areas of Liverpool twice the national average. We have shown that increasing numbers of HNC are associated with human papillomavirus (HPV) infection. HPV is a double-stranded DNA virus that can integrate into host DNA and inactivate tumour suppressor proteins. For reasons currently not well-understood, patients with HPV+ tumours have better outcome in terms of both survival and reduced risk of recurrence compared with HPV- HNC. We hypothesize that this observation reflects a greater intrinsic immunogenicity associated with HPV infection, pertaining to immune system pathways activated following recognition of viral nucleotide compounds. One such novel pathway is the Stimulator of Interferon Genes (STING), a recently discovered pathway that forms a central component of our response to infection- sensing parasitic, bacterial or viral DNA in the cytosol and inducing type-I Interferons in response.
HNC provides a unique model to study the STING pathway in the context of virus-induced tumour. The aim of this project is to understand how STING activity is differentially regulated in HPV+ and HPV- HNC and evaluate the potential of this pathway as a target to potentiate anti-tumour immune responses.
Qualifications and Experience
Applicants should have, or expected hold first class or upper second class honours degree (or equivalent) in biomedical sciences or relevant field and some laboratory research experience. You may have additional Masters level research experience in cell biology, immunology or cancer research.
Applicants must satisfy the appropriate University English language requirements. For EU students, this is an IELTS score of 6.5 with no band score lower than 5.5.
To apply please send your CV, cover letter and the names and addresses of two references to Dr L Dahal: [Email Address Removed]
This 3-year PhD studentship covers tuition fees, research support costs and a stipend at UKRI standard rates (£15009 p.a. for 2020/21). Due to limited funding, the studentship is only open to UK and EU candidates.