Deputy programme leader: Dr Lara Friedlander
Understanding diseases in order to improve diagnosis and treatment
Our aim is to investigate the cellular, and molecular basis of oral diseases, and their treatment.
We focus our work in three areas:
- Oral mucosal disease (including squamous cell carcinoma)
- Periodontal diseases
- Angiogenesis and tissue regeneration
Immunopathological mechanisms underpinning oral mucosal diseases
Microenvironment of oral cancer
We are integrating our investigations into various factors associated with oral squamous cell carcinoma (OSCC), to develop a greater understanding of the tumour microenvironment. This includes assessment of the tumour cells themselves but we are particularly interested in the communication between tumour cells, local immune cells and vascular and lymphatic cells.
Regulation of immune responses in oral diseases
OSCC develops in an immune cell-rich environment, where inflammatory cells in the tumour microenvironment establish an anti-tumour response by secreting pro-inflammatory cytokines. At the same time the cancer cells may induce various mechanisms suppressing the anti-tumour response such as regulating a network of suppressive cytokines and the recruitment of suppressive Tregs. These escape mechanisms are seen at the local tumour site and similar mechanisms may also occur in regional lymph nodes (LN). A current project is investigating the concept that the escape of malignant oral keratinocytes from the primary site and their metastasis to regional lymph nodes is orchestrated by regulatory T cells and their associated immune repertoire.
Oral lichen planus (OLP) is a common chronic immune-mediated disease. We are comparing the number of cells expressing various immune markers in OLP with non-specifically inflamed oral mucosa using immunohistochemistry and determining gene expression with quantitative real-time reverse transcriptase polymerase chain reaction.
Angiogenesis and lymphangiogenesis
We have shown that angiogenic factors were expressed on epithelial cells as well as endothelial cells in OSCC. These findings offer an insight into upregulation of pro-angiogenic genes in oral cancer. In the future, anti-angiogenic therapies in OSCC could prove to be useful as an adjunct to conventional surgical and chemotherapeutic treatments.
We are investigating angiogenesis, growth factor and cytokine activity in pulp biology in relation to pulp-dentine development and response to injury. In particular, the apex of immature permanent teeth has been shown to contain a rich source of angiogenic factors which may contribute to development and healing. The impact of Type 2 Diabetes on the dental pulp is a further area of investigation and our findings indicate that there are distinct histological and immunological differences in the pulps of healthy and diabetic patients. This is clinically significant and may suggest that there are similar processes happening in dental tissues to elsewhere in the body.
Deer antlers are the only known mammalian appendages that can annually achieve complete epimorphic regeneration. We are investigating the wound healing and regenerative potential of deer antler, in what is a stem cell based regeneration model, focusing on pleiotrophin, one of the highly up-regulated transcripts.
Endoplasmic reticulum stress in oral diseases
Cellular stress pathways known as the unfolded protein response (UPR) are activated when the endoplasmic reticulum, the protein-producing factory within the cell, is stressed. ER stress modulates UPR pathways, thus partially determining the cellular responses to disease. Evidence suggests that UPR components are activated to either inhibit cancer growth or promote its progression and this is being investigated in a series of projects. The affect on UPR in periodontal ligament cells subjected to mechanical strain, mimicking orthodontic tooth movement is a further area of study.
Our Oral Molecular and Immunopathology programme profile (PDF extract from 2017-18 SJWRI Research Report, 1.1 Mb) contains more details on our current research projects, collaborations funding highlights and recent publications.