Laboratory head: Dr Tom Karagiannis
The discipline of epigenomics represents the merged science of epigenetics and genomics. The ultimate aim of this field is to map and unravel the biological and biomedical significance of epigenetic phenomena. The term epigenetics was introduced by the British scientist Conrad Waddington in the 1940s to incorporate all of the factors controlling gene expression and cell differentiation. It was derived from the virtually redundant Aristotelian word of epigenesis, which was used by the Hellenic philosopher to describe his theory of gradual and progressive developmental changes.
Today, epigenetics is typically defined as inherited phenotypic changes that are not due to changes in gene sequence. However, an expanded approach may be to refer to epigenetics as an integrative view of the cellular and molecular mechanisms governing DNA metabolic processes including transcription, replication and repair.
The aim of the EpiMed (Epigenomic Medicine) laboratory is to investigate epigenetic modifications and responses in models of human disease, particularly chronic progressive conditions such as cardiovascular disease, diabetes and cancer. A further aim is to develop pharmacologic and dietary interventions, targeting genetic and epigenetic marks of disease. More specifically, research in the laboratory is focussed on three distinct but complementary directions:
- Epigenetic markers of DNA damage in ageing and disease.
- Genetic and epigenetic modulation using dietary polyphenols and chromatin modifying compounds.
- Nanoparticle-targeted therapeutics and imaging agents.
Epigenetic markers of DNA damage in ageing and disease
gammaH2AX as a molecular marker of DNA double-strand breaks
Phoshophorylation of the Ser-139 residue on the histone variant H2AX, forming gammaH2AX, represents a highly sensitive marker of DNA double-strand breaks. Following induction of double-breaks nuclear gammaH2AX foci form which are easily visualized and quantitated by immunofluorescence.
We explore gammaH2AX in disease process and we utilize this marker to investigate cellular responses to DNA damaging agents.
Genetic and epigenetic events in diabetic wound healing
The normal wound healing response is a complex process involving numerous cell types. It is typically associated with three main phases, 1) acute inflammation, 2) proliferation and 3) remodelling. Impaired wound healing in diabetes is usually the result of angiopathy or neuropathy. Aberrant inflammatory responses, angiogenesis, reepithelialisation and keratinocyte and fibroblast migration have been associated with impaired diabetic wound healing.
We investigate genetic and epigenetic variations using cell-based models of diabetes and next generation sequencing technologies.
Genetic and epigenetic modulation using dietary polyphenols and chromatin modifying compounds
Biological evaluation of olive polyphenols in models of disease
The medicinal properties of the leaves and fruit of Olea europaea (olive tree) have been known since antiquity. Evidence indicates that the Cretans have been cultivating olive trees and using olive oil for over 3000 years. Modern research is indicating that the polyphenols, such as hydroxytyrosol, are the most likely candidates accounting for the cardioprotective and cancer preventative effects of extra virgin olive oil.
We are investigating the biological effects and molecular mechanisms of action in cellular models of human disease using a wide-range of biochemical assays as well next generation sequencing technologies.
Nanoparticle-targeted therapeutics and imaging agents
Receptor-specific imaging using nanoparticles
We are developing receptor targeting nanoparticles incorporating a DNA binding ligand for diagnostic imaging applications. Given the finite number of receptors on target cells, the rationale is to improve the resolution of imaging with the use of a DNA binding ligand.
Dr Simon Royce
Jane Jisun Sung