About Epigenetics in Human Health and Disease
It is increasingly appreciated that gene-environment interactions particularly as they pertain to human health and disease involve epigenetic pathways including a range of biochemical modifications of chromatin including DNA methylation are key areas of interest. The central focus of the research team is to investigate the mechanisms by which specific epigenetic changes including chromatin modifications serve to integrate the transcriptional responses to distinct signaling pathways. The rapid rate of progress over the past five years and the series of discoveries that we and others have contributed in the field concerning epigenetic modification and gene regulation reflect unheralded advances in understanding human development and disease.
We are interested in characterising the functional roles of specific components critical in gene regulation and examining the link to human disease using genetic, epigenomic and molecular approaches. The group led by Professor El-Osta is interested in understanding the roles of specific transcriptional components in the regulation of metabolic memory and cardiac disease and further extending our understanding of gene silencing events associated with genomic methylation in preclinical models and human populations. The focus of the laboratory is to provide fundamental insights into the mechanisms by which epigenetic changes and associated chromatin modifications control genes implicated in human health and disease.
Our investigation of the molecular mechanisms of gene regulation by specific repressor and co-activator complexes using vascular endothelial and cardiac cells as well as the brain, has led to a range of novel mechanistic insights into the biology of epigenetic changes mediating critical transcriptional changes in models of endothelial dysfunction, vascular disease and in utero programming. Professor El-Osta’s and his ream have contributed to understanding the molecular mechanisms whereby epigenetic changes exert positive and negative transcriptional functions in specific model systems. His team explores the relationship between different classes of co-repressor and activator complexes and the regulation of chromatin remodelling events in maintaining gene expression implicated in disease.