22 Aug 2018

Spotlight on our NHMRC Fellowship winners: Professor Sam El-Osta

Professor Sam El-Osta
Department of Diabetes, CCS
by Anne Crawford

Professor Sam El-Osta. Senior Research Fellowship: characterise novel epigenetic mechanisms and the exact nature of ‘metabolic memory’ at sites of diabetic complications.

Professor El-Osta’s Fellowship project is building on his previous exciting findings about epigenetic modifications – the chemical changes that modify DNA – and will target genes that are implicated in diabetic nephropathy and atherosclerosis.

He is investigating epigenetic pathways that regulate gene behaviour which involve mechanisms involving the direct methylation of DNA and histones. Methylation is a process that regulates the way our genes behave like an on/off switch, regulating gene expression.

Professor El-Osta’s research links DNA methylation with diabetic kidney disease, and histone methylation with diabetic cardiovascular disease.

“The key objective of this research fellowship will be to further develop the molecular basis of what is referred to as ‘metabolic memory’,” he said.

Genes can be hardwired to ‘remember’ glucose, which is referred to as ‘hyperglycaemic memory, and this epigenetic persistence or memory plays an important role in diabetic complications.

“Epigenetic changes hardwire specific genes by ‘writing’ these tiny chemical marks that involve the methylation of DNA and histones,” Professor El-Osta said.

The research will advance work into a prototype drug used previously by Professor El-Osta’s group that can erase histone methylation by targeting specific epigenetic enzymes such as Set7. The researchers revealed the Set7 methyltransferase “sets the scene” in regulating key target genes important in the progression of diabetic complications – a landmark finding as it was the first epigenetic enzyme to be associated with diabetic complications.

Professor El-Osta anticipates that this area of research could ultimately have a major impact on the way clinicians manage transient hyperglycemia, emphasising strategies to reduce glucose fluctuations and to identify targets for new approaches to reduce the cardiovascular and renal burden associated with diabetes.

Professor El-Osta, a transcriptional biologist specialising in epigenetics, leads a research group in the Department of Diabetes. He has contributed more than 200 articles and publishes internationally recognised research. Awards include the AMGEN Australian Medical Researcher of the Year and the JDRF Early Career Research Award for Innovation. He is vice-president of the International Epigenetics Society, on the editorial board of Circulation Research and Epigenetics, and serves as Chair and Organiser of the Gordon Research Conference on Epigenomics of Diabetes.

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