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Effect of valproic acid on the gene regulatory landscape of gingival mast cells. A potential role for treatment of dental periodontitis

Code: BC-DTP_2026_17

Title: Effect of valproic acid on the gene regulatory landscape of gingival mast cells. A potential role for treatment of dental periodontitis.

Primary Supervisor: Fabian Flores-Borja

Email: f.flores-borja@qmul.ac.uk

Institute: Institute of Dentistry

Secondary Supervisor: Diego Villar Lozano

Email: d.villarlozano@qmul.ac.uk

Institute: Blizard Institute

Lay Summary:

Periodontitis, or gum disease, is a chronic inflammatory condition that develops when bacteria grow on the surfaces of our teeth. If untreated, periodontitis damages the gums, destroys tissues supporting the teeth, and causes tooth loss. Periodontitis is a major public health problem, affecting around 14% of adults worldwide (more than one billion cases), and has been linked to serious diseases, including diabetes, arthritis, and heart disease. On the local level, 77% of residents in the Tower Hamlets borough have some form of gum disease, a rate higher than the national average, and among older adults, 16% present with severe disease. One reason gum disease is hard to treat is that standard dental treatments do not fully control the body’s immune reaction driving the inflammation. While immune cells have been associated with periodontal disease, there is limited information on the role and of mast cells (a type of blood cell associated with allergy), which are thought to initiate and maintain the inflammation that leads to destruction of tooth-supporting tissues. In this project, we will investigate whether valproic acid (VPA), a compound first introduced in the early 1960s for the treatment of epilepsy can control the pro-inflammatory activity of mast cells by modifying the range of genes activated during periodontitis. The overall objective of this project is to gather evidence on the ability of VPA to regulate inflammation in gum tissue. A positive effect could contribute to restoring a healthy tissue state in patients with periodontitis – a condition over-represented in East London.

Aims:

Experimentally, this project is divided in four main aims/objectives:

  1. Generation of mouse gingiva-derived MC and in vitro characterisation of the effect of VPA on MC function.
  2. Characterisation of the VPA-mediated epigenetic regulation in mouse gingival MC.
  3. Establishment of a mouse model to analyse the effect of VPA administration on the clinical manifestations of periodontitis.
  4. Effect of VPA on the local and distal immune landscape

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