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The oral microbiome, ROS and the development of oral cancer: a role in Fanconi anemia?


Project Description

Many patients with Fanconi Anemia (FA) develop cancers of the mouth, esophagus or anogential region. A number of reasons have been suggested, but the millions of bacteria that are naturally resident in these body sites might be a significant contributory factor. In the mouth, FA patients are prone to severe gingivitis and periodontal disease caused by these resident bacteria. We have preliminary data that shows that key components of one of these periodontitis-causing bacteria can damage the DNA of mouth lining cells and that this damage is not efficiently repaired in cancer cells derived from FA patients. As cancer develops in cells with damaged DNA, this may give valuable insight as to why FA patients often develop oral, esophageal or anal cancers. In this project we will extend our research to further assess the damage to the DNA using a range of oral bacteria and derived virulence components in order to identify agents that could be used to prevent DNA damage occurring in the first place. If successful, such agents could be readily extended into patients with trials of preventative drugs as a strategy of improving oral health. This may lead to changes in the standard of care for FA patients, and potentially help reduce oral cancer incidence in FA patients.

Overall Hypothesis:
DNA damage caused by components of the oral microbiome is a major contributory factor in the development of oral cancer, particularly in patients with Fanconi Anemia.

This project aims to address the following objectives:

1. To extend our preliminary investigation of the effects of oral pathogenic bacteria on DNA in cancer cells using a wide range of virulence factors and live cells.
2. Use CRISPR/CAS9 to generate FANC-deficient normal oral keratinocytes (NOKs) for assessment of the effects of bacteria on a more physiologically relevant starting cell.
3. To explore methods of inhibiting bacterial-mediated DNA damage using anti-oxidants or strategies aimed at altering the oral microflora

Enquiries:
Interested candidates should in the first instance contact (Professor Keith Hunter )

How to apply:
Please complete a University Postgraduate Research Application form available here: http://www.shef.ac.uk/postgraduate/research/apply

Please clearly state the prospective main supervisor in the respective box and select School of Clinical Dentistry as the department.

Funding Notes

This project is open to self-funded students only.

Related Subjects

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