Infection, Immunity and Inflammation
The Infection, Immunity and Inflammation Research Group aims to improve the understanding of the biological mechanisms of microbial and immune mediated oral disease, thereby improving diagnosis, classification and treatment. It has two main themes: Molecular Microbiology and Infection, and Mucosal Immunology and Inflammation.
The Molecular Microbiology and Infection theme investigates:
- Mechanisms and consequences of dysbiosis of the oral microbiome with particular reference to periodontal disease, implant infection and oral malodour.
- Development of novel antimicrobials, including those based upon nanotechnology and funded by Innovate UK, for the prevention and treatment of oral infection.
The Mucosal Immunology and Inflammation theme investigates:
- The biology of inflammation and innate and adaptive immune systems operating within the oral mucosa in health and disease.
- The mechanisms that regulate oral mucosal repair and oral epithelial barrier function.
- The interplay with the immune system and microbial virulence factors implicated in orchestrating inflammation in periodontal disease.
- The interaction of genetic and environmental factors on development of inflammatory oral disease and the systemic consequences.
- Efficacy of immunotherapies in treating inflammatory oral diseases.
The research themes benefit from strong industrial collaborations, well established clinical collaborations with the London Behçet’s Centre of Excellence and interdisciplinary links across Queen Mary and beyond. The laboratory research is undertaken within the award winning Blizard building.
Early cancer diagnosis and novel therapies
Oral squamous cell carcinoma (OSCC) is difficult to treat because the majority of them arise without any visible pre-malignant lesion. Furthermore, at present there are no effective treatments for advanced OSCC other than surgery and radiotherapy/chemotherapy. However, genetic and transcriptomics data has established that OSCC does arise from a subset of dysplasias when these lesions are detected1,2. Using approaches such as mutation analysis of genes involved in the breakdown of cellular senescence1, extracellular molecule detection (Figure 1)
Figure 1 Summary of the extracellular metabolites in low risk pre-malignant oral lesions LRPPOL, high risk pre-malignant oral lesions (HRPPOL) and normal keratinocytes.
The figure summarises the key extracellular metabolites that change in LRPPOL and HRPPOL keratinocytes relative to normal oral keratinocytes. Boxes in red indicate a statistically significant increase of pathways or individual metabolites relative to normal and boxes in green indicate a statistically significant decrease.
FOXM1-based digital molecular cancer test - "quantitative malignancy diagnostic index system (qMIDS3 –Figure 2)", we aim to distinguish between high and low risk pre-malignant lesions with the subsequent aim of developing liquid biopsy4 assays for early stage OSCC. The development of liquid biopsy tests for OSCC could greatly assist the detection of oral cancer in its early stages and thus with modern imaging techniques allow the reduction of surgery with the consequent reduction in costs and morbidity.
Figure 2 The qMIDS digital cancer test.
The qMIDS test requires only a tiny 1 mm (a grain of rice) tissue biopsy and test results could be obtained within 90 mins by measuring 16 genes to produce a malignancy index via an algorithm3. The qMIDS test has been validated on several hundreds of oral cancer patients from UK, Norway, China and India with highly accurate results (>90%) compared to conventional histopathology3,5.
Hunter, K. D. et al. Divergent routes to oral cancer. Cancer Res. 66, 7405-7413, doi:10.1158/0008-5472.CAN-06-0186 (2006).
Hunter, K. D., Parkinson, E. K. & Harrison, P. R. Profiling early head and neck cancer. Nat. Rev. Cancer 5, 127-135, doi:10.1038/nrc1549 (2005).
Teh, M. T. et al. Exploiting FOXM1-orchestrated molecular network for early squamous cell carcinoma diagnosis and prognosis. Int. J. Cancer 132, 2095-2106, doi:10.1002/ijc.27886 (2013).
Qadir, F. et al. Transcriptome reprogramming by cancer exosomes: identification of novel molecular targets in matrix and immune modulation. Mol. Cancer 17, 97, doi:10.1186/s12943-018-0846-5 (2018).
Ma, H. et al. Independent evaluation of a FOXM1-based quantitative malignancy diagnostic system (qMIDS) on head and neck squamous cell carcinomas. Oncotarget 7, 54555-54563, doi:10.18632/oncotarget.10512 (2016).
Tissue Repair & Regeneration
Within the theme of tissue repair and regeneration we are privileged to have expertise in both preclinical and clinical research in the field of soft and hard tissue regeneration in healthy and systemic diseases such as diabetes and osteoporosis. We have published a number of studies where the genetic and proteomic expression of bone regeneration and osseointegration has been extensively evaluated and allows us to have a comprehensive understanding of these biologic processes.
The impact of the genetic background, the utilization of imaging techniques to review the non surgical and surgical periodontal healing, the treatment of peri-implant diseases and the introduction of minimally invasive treatment procedures are also an integrated part of this research theme.