Epigenome Maintenance & Ageing
To understand the epigenetic changes we see in disease and in response to our environment, we must first understand how the epigenome is maintained and how 'epimutations' can arise with ageing. My work has examined the genomic targets of DNA methyltransferase (DNMT) enzymes and epigenetic models of ageing.
Genomic targets of DNMTs
As part of a collaboration led by Dr Chanachai Sae-Lee and Dr Hyang-Min Byun (Newcastle University), my work has helped to identify the unique and shared targets of 13 DNMT isoforms (Sae-Lee et al, 2022, Clinical Epigenetics).
We identified loci that are uniquely methylated by single DNMT isoforms, while reporting that most loci do not display such isoform-specificity. We demonstrated that dietary constituents such as caffeic acid can be used for isoform-specific inhibition in vitro.
Epigenetic models of ageing
Over the past decade there has been an explosion of interest in epigenetic models of ageing, such as the Hannum model and the 'epigenetic clock' developed by Horvath. These have shown associations with the risk of developing cardiovascular disease and cancer, and all-cause mortality. However, there remains much that we do not understand about these models and what they truly represent.
My ongoing work explores epigenetic ageing and how this relates to cancer risk.