El-Osta research group
Key terms: Clinical and Molecular Epigenetics, Chromatin, DNA and RNA methylation, Histones, Transcriptional Regulation, Human Disease, Computational Epigenomics
- Understand mechanisms of transcriptional control in metabolic disease
- Novel epigenetic discoveries in diabetes and its complications
- Set7 as a novel therapeutic target in vascular disease
Feb 2017 El-Osta group. L-R: Dr Jun Okabe, Mr Harikrishnan Kaipananickal, Dr Mark Ziemann, Mr Antony Kaspi, Ms Hanah Rodriguez, Dr Ishant Khurana, Dr Gulcan Sarila, Mr Sameer Jadaan, Prof Sam El-Osta, Dr Haloom Rafehi, Mr Scott Maxwell, Ms Nazanin Karimnia
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 my 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 characterizing the functional roles of specific components critical in gene regulation and examine 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 extend our understanding of gene silencing events associated with genomic methylation in pre-clinical 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 laboratory, has 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 remodeling events in maintaining gene expression implicated in disease.
- Building scientific excellence and expanding knowledge and discovery in the field of epigenetics, transcriptional regulation and metabolism. References: Circulation Research│Molecular Aspects of Medicine│Circulation
- Training and education in the major technologies of contemporary epigenomics research in vascular disease and clinical-epigenetics. References: Genome Research│Epigenetics
- Understanding the role of oxidative stress in mediating diabetes-associated epigenetic modifications. References: The Journal of Experimental Research│Diabetes
- Understanding the role of epigenetic changes in diabetes and cardiovascular risk. References: Circulation Research
- Characterizing the role of Set7 methyltransferase. References: Circulation Research│Nucleic Acids Research
- Exploring new regulatory models implicated in pre-clinical models of disease. References: Nucleic Acids Research
- To determine the role of chromatin modifications in the context of ncRNAs and understand the opposing roles of the MeCP2 regulatory complex in the control of gene expression patterns in the brain. References: Nature Genetics│Journal of Neuroscience
- Epigenetic differences associated with cardiovascular disease. References: Arteriosclerosis, Thrombosis, and Vascular Biology│JCI Insight│Neuroscience & Biobehavioral Reviews
Projects and Opportunities
- Epigenetics of diabetes, mapping the human methylome and building the epigenomic atlas of Type 1 Diabetes
- ncRNAs and histone code changes mediate epigenetic events and gene expression in heart disease
- MeCP2 interacting ncRNAs associated with gene regulatory changes
- Set7 methyltransferase as a target to reduce the burden of diabetic vascular and renal complications
- ROS mediated epigenetic changes associated with hyperglycemic memory
Current project funding
Pubmed link [El-Osta+A]. See feed of Monash University validated publications and projects below.