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Exploring the role of histone deacetylase inhibitors as regulators of innate immune cells activation in periodontitis


Institute of Dentistry

About the Project

Second Supervisor: Rommel Chacon-Salinas (National Polytechnic Institute, Mexico)

Background:

Oral diseases (including dental caries, periodontitis, and oral cancer) are the most common non-communicable diseases representing a public health problem affecting 20-50% of the global population in both developed and developing countries (1). Oral diseases affect people throughout their lifetime, causing pain, discomfort, disfigurement and even death. Periodontitis, the 11th most prevalent oral disease globally (2), is a chronic inflammatory disease characterised by the destruction of alveolar bone and connective tissue structures that supports teeth (3). The most common treatment for periodontitis is the mechanical removal of biofilm and plaque-retentive factors. This is a long-term professional, and expensive, treatment requiring mechanical debridement and on many occasions surgical access and the use of grafts to prevent tooth loss. In addition, the main tissue destruction observed is due to an exacerbate host response, which is usually not directly targeted with the traditional therapy approach. Periodontitis is strongly associated with the infection with Porphyromonas gingivalis (P. gingivalis) that leads to alterations of the oral microbiome and subsequent chronic activation of different cellular components of the immune response (4). Mast cells reside in several vascularized tissues, such as the oral cavity and can secrete different inflammatory mediators after recognizing bacterial pathogens, including P. gingivalis. Recent studies have demonstrated that mast cells are increased in the gingiva of patients with chronic periodontitis and their activation correlates with disease severity (5-7).

Aims:

In this project, we will set in vitro protocols and animal models of periodontitis to characterize gingival mast cells and evaluate the effect of histone deacetylases inhibitors (HDACi) for treatment of periodontitis. Among different HDACi, we will focus on valproic acid (VPA), which has been recently used in the treatment of patients with cancer due to its ability to modulate the activation of innate and adaptive immune cells, including macrophages, dendritic cells, neutrophils, NK cells, B and T lymphocytes (8).

How to apply:

For more information regarding the project, please contact: Fabian Flores-Borja ()

Applications should be submitted through the Queen Mary application system. Please indicate the project title and supervisor in the ‘Research Degree Programmes - Additional Questions’ section of the application.

Alongside the application form, please send the following supporting documents:
• Curriculum Vitae (CV)
• Copies of your degree certificates with transcripts
• Proof of English language ability for overseas applicants from non-English speaking countries
• A one-side A4 statement of purpose. This should set out your previous academic or other experience relevant to the proposed research; why you wish to undertake this research at QMUL; your previous research or professional training and what further training you think you will need to complete a PhD; and what ethical issues you will need to consider in undertaking this research.
• Two references. At least one reference must be from an academic referee who is in a position to comment on the standard of your academic work and suitability for postgraduate level study. Where appropriate, a second referee can provide comment on your professional experience.

Please contact with any queries about the application process.

Funding Notes

Person specification:
A graduate with at least an upper second class honours degree or a distinction in an experimental MSc degree. The candidate should have strong interests and preferably with some experience in molecular pathology, infectious diseases, microbiology, immunology or animal models work. Would best suit a clinician/scientist with an interest in dentistry and oral diseases.

Funding notes:
Both self-funded and sponsored students will be considered if they have funds to cover tuition fees and bench fees for three years full-time or six years part-time. UK/EU students might be eligible for tuition fees and stipend from Student Finance England: View Website

References

References:
1. World Health Organisation. Key Facts. https://www.who.int/news-room/fact-sheets/detail/oral-health.
2. Tonetti MS, et al. J Clin Periodontol. 2017. 00:1-7.
3. Malcolm J, et al. J Dent Res. 2016. 95: 704-10.
4. Konopka L, et al. Int J Immunopathol Pharmacol. 2010. 23: 803-10.
5. Agrawal R, et al. 2016. 20:91-5.
6. Huang S, et al. J Periodontol. 2013. 84:248-55.
7. Batista AC, et al. Oral Dis. 2005.11:249-54.
8. Soria-Castro R, et al. J Immunol Res. 2019; 2019:1–24.

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