Pathobiology of head and neck cancer (various projects available)

Description

A PhD studentship is available in Professor Keith Hunter’s laboratory in the Liverpool Head and Neck Centre (https://livheadandneck.co.uk/).  Prof Hunter’s laboratory undertakes studies in the various stages of the development of head and neck cancer (HNSCC) and evaluates these using in vitro and in vivo studies in preclinical models and patient tissues. The ultimate aim of the group is to improve our understanding of mucosal head and neck cancers in terms of their development, progression and responses to therapy.

A number of potential projects are available which can be matched to the applicant’s skills and interests.  These include:

1. Modelling radioresistance and chemoradioresistance in HNSCC. The development of resistance to oncological therapies in HNSCC is a significant issue, particularly in the recurrent/metastatic setting.  Treatment of these patients is challenging, and prognosis is poor.  We have developed cisplatin-resistant clones on HPV+ and HPV- OPSCC cells which show significant alterations in the number of cellular processes.  This project will focus on the development of radioresistant and chemoradioresistant cells to identify the key pathways mediating this resistance and to identify therapeutic strategies to overcome resistance.
2. A return to p53: mutational status, clinical outcome and therapeutic potential of nonsense mediated decay inhibition in HNSCC. Mutations in p53 are the only mutational event consistently present in >25% of all HNSCCs. Truncating mutations arise as a result of the mutation generating a STOP codon.  Many of these truncated mRNAs are not translated to protein and are removed from the cell by the process of Nonsense Mediated Decay (NMD): cells with a premature STOP codon do not express p53 protein, and the function of p53 is lost.  This project will focus on NMD in HNSCC and in particular, how that relates to p53 expression and function. NMD inhibitors may allow for the re-expression of p53 in HNSCC which may restore p53 function in these cells.
3. Defining the clonal evolution of oral epithelial dysplasia (OED). Understanding the molecular evolution of oral potentially malignant disorders (OPMDs) is a key part in defining effective treatments for these lesions. Many of the molecular events in OPMD/OED development have been described in isolation:  for example, p53 is mutated and p16 expression is lost. How these features relate to the overall alterations to the genome and transcriptome in time and spatially within the tissue is not known.  Detailed sequencing of a large cohort of OPMDs has not been undertaken, but it is assumed that the spectrum of changes will be similar to that identified in OSCCs.   Techniques for the assessment of the genome and transcriptome in intact tissue are now available and these can be applied in this project to the questions of molecular heterogeneity in OPMDs as they develop, how this relates to the mutational profile and what further changes are present at the very early stages of invasion.

Informal enquiries are very welcome to discuss these projects:  please email Professor Keith Hunter (keith.hunter@liverpool.ac.uk).

Please send CV and covering letter to Professor Keith Hunter: keith.hunter@liverpool.ac.uk