Driving cutting-edge molecular discoveries
The Oral Health Theme aims to apply cutting edge molecular discoveries in tooth restoration and replacement, hearing loss, and mucosal disease. Programmes include tooth regeneration, restoration of sensorineural hearing loss, and preventing fungal pathogenesis caused by Candida.
Our research is delivered through 3 programmes:
- Programme 1. Tooth repair and regeneration and oral soft tissue restoration
- Programme 2. Craniofacial sensory organ repair and regeneration
- Programme 3 Oral fungal infections
- Towards bioengineered, natural tooth fillings Current dental treatments of deep filings replace living tissue with inert cements and metals and often rely on mercury-containing fillings or entirely replacing teeth with implants. Our new restorative therapies stimulate the Wnt pathway, encouraging stem cells in the decayed tooth region to turn into dentine, the natural, living filling of healthy teeth. LithGlass uses lithium ions within a tooth cement (glass ionomer) for shallow fillings, whereas ReDent uses a repurposed small molecule drug to stimulate Wnt signalling in deeper fillings. The nature of the treatment means that doses are low and highly localised. We have also developed nanoneedles that can provide targeted delivery of molecules to activate the tissue-resident stem cells to trigger regeneration. Phase 1a/b clinical trial is planned for 2022. (Zaugg LK. et al (2020) J. Dent. Res. 99, 544-551; Alaohali A (2022) J. Dental Res. Jan;101(1):46-53)
- Therapies to restore hearing Although cochlear implants and bone-anchored hearing aids are successful, they are not suitable for all forms of deafness and do not restore normal hearing. We are studying the mechanisms of hearing cell loss to develop therapies that can restore damaged tissue and identify new candidate deafness genes from human populations. There are numerous challenges to delivering drugs to the inner ear and part of our programme of work is developing advanced formulation technology (Lewis, MA. (2018) BMC Medical Genomics 11:395; Fons JM. (2020) Development 147: 23)
- Oral fungal infections Deaths per annum from fungal infections are greater than the global mortality due to malaria or breast cancer and are similar to deaths due to tuberculosis or HIV. Our work covers the human fungal pathogen Candida albicans, the causative agent of thrush which causes millions of infections annually worldwide. We have discovered that the invasive (hyphal) form of C. albicans secretes a cytolytic peptide toxin, named candidalysin (Naglik JR. et al., (2019) Curr Opin Microbiol. 2019;52:100-109). Studying how candidalysin acts in disease will help to better understand the biological processes that promote fungal pathogenesis and host immunity and to translate this knowledge into the development of novel immunotherapies, vaccines and diagnostics.