Research in the Division
Mucosal surfaces are the bodies interface with the external environment and must be protected against environmental chemical, physical and infectious insults in order to prevent disease. Protection of the oral mucosal surfaces is provided saliva and the secretory/mucosal immune system.
(Photo above: Candida albicans hyphae invading into oral epithelial cells - see arrow)
Our research aims to understand pathogen interactions at mucosal surfaces and examines basic immunological responses to exogenous stress, immunopathology of autoimmune mucocutaneous disorders and the role of bacterial toxins in the development of cancer.
A major cause of mucosal disease is cancer and researchers in the group undertake a broad range of cancer research including epidemiology and screening, diagnostics, natural history of oral potentially malignant diseases (Precancer), the role of human papilloma virus in aetiology and treatment outcome, DNA ploidy analysis for precancerous lesions of the mouth, pharynx and lower oesophagus, and into a range of molecular biomarkers. In basic studies we are developing molecular tools for early diagnosis and prediction of responses to radio and chemotherapy. The molecular genetic pathways commonly deregulated in head and neck cancers (eg. the p53 family, inhibitors of apoptosis proteins and EGFR) are being examined. We are investigating these pathways as possible therapeutic targets for the development of small molecule inhibitors, monoclonal antibodies, peptides and microRNAs.
Saliva presents the first line of defence against infection and researchers are examining how salivary components enable saliva to be such an effective protector and maintainer of oral health. Large numbers of people suffer from chronic oral dryness due to effects of disease or medication on the function of salivary glands and our research aims to understand the mechanisms of salivary gland dysfunction and how functional glands may be recovered or regenerated. Saliva is being increasingly being recognised as a non-invasively collected biofluid for the diagnosis of both oral and systemic disease and our research is investigating the application of salivary diagnostics.
The development of interventions to prevent HIV-1 infection including both microbicides (topically applied inhibitors) and vaccines (using an allo-immune strategy). Research in these topics is carried out as part of large international collaborative projects.
Investigation of epithelial signalling pathways, stimulated by the fungal pathogen Candida albicans and by HIV-1. This research has identified mechanisms that distinguish commensal and pathogenic states allowing for maintenance of homeostasis or stimulation of protective immunity.
Investigation of immunopathogenesis and biomarkers of mucous membrane pemphigoid, Sjogrens Syndrome, orofacial granulomatosis and other mucosal diseases. Research in these topics benefits from access to a large cohort of patients.
Head and Neck Cancer
Data mining of the available human microbiome information that is now available to identify novel host pathogen interactions, based on the increasing realisation that heart disease, ageing and cancer could also have a bacterial aetiology.
Analysis of the cellular effects of a class of bacterial toxin that interferes with normal host cellular signalling in a way that mimics tumour progression. Clinical and lab based analysis of the role of one toxin that is a likely candidate for involvement in human cancer.
Probing the interconnections between eukaryotic signalling pathways using bacterial toxins, taking advantage of their highly specific mode of action.
Tumour specific induction of cell death by the viral proteins Apoptin and E1A and identification of tumour specific kinases .
Development of novel gene and protein delivery systems including secretable protein transduction peptides and polymers.
Combination therapy using novel targeted agents including TRAIL and inhibitors of IAPs (SMAC mimmetics)
Identification of the mechanisms of response to radio- and chemo-therapeutic agents in human papillomavirus associated oropharyngeal cancer in order to exploit these pathways to improve the management of all head and neck cancers.
Role of p53 family members including p73 and p63 in cancer metastasis and resistance to therapies
Identification of molecular markers including microRNAs predictive of radioresistance in head and neck cancers.
Collection and banking of saliva for use as a diagnostic tool in a range of oral and non-oral diseases including periodontal disease, H&N squamous cell carcinoma. Studies with UK Biobank.
Formation and composition of saliva films on oral surfaces and their impact on oral function including food perception, hard tissue mineralization and mucosal wetness.
The changes in saliva and the oral mucosa leading to chronic oral dryness and the diagnosis and monitoring of disease in dry mouth patients.
The use of minimally invasive surgery to treat patients with salivary gland disease including obstructive and cancer.
The mechanisms leading to chronic salivary gland disease and loss of function and obstruction
The role of salivary stem cells and signalling mechanisms in glandular regeneration following disease and radiation induced atrophy.