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Interview with Dr Michelle Thunders, senior lecturer in the Department of Pathology and Molecular Medicine at the University of Otago, Wellington.

Identifying epigenomic biomarkers as potential predictors of disease or indicators of susceptibility in young MI patients

POSTED: 20 February 2018

Dr Michelle Thunders is a senior lecturer in the Department of Pathology and Molecular Medicine at the University of Otago, Wellington. In 2017 she received a $27,700 research grant to undertake research to help identify cardiac biomarkers in young patients presenting with myocardial infarction (MI).

Describe your particular passion for why you are researching?

Globally, ischaemic heart disease is a major contributor to premature morbidity and mortality and is associated with significant economic burden.  Mortality from Myocardial Infarction (MI) has improved due to advancements in pharmaceuticals and medical care, however, incidence of MI remains high with a significant proportion of new MI patients presenting as young patients, typically under the age of 55. A recent study by Matsis et al described the clinical characteristics of 1199 patients on the Wellington Acute Coronary Syndrome registry. In this cohort 12.8% (154/1199) of the patients presented with MI as young patients. Of this group 36% had none or only one traditional risk factor for MI prior to presenting with their index coronary event and so would have been classified as ‘low cardiovascular risk’. 10% of MI patients typically have further events (recurrent myocardial infarction, stroke or death) in the year following the index event, the identification of biomarkers which can assist in the identification and management of young MI patients at increased risk of poor outcomes is therefore needed.

Why are you doing this particular research?

To help aid in management and rehabilitation of young ‘low risk’ individuals who have already presented with MI.

Epigenomic biomarkers are increasingly used in medical diagnostics. Unlike DNA sequences, largely the same in every cell, epigenomic changes can occur as a result of dietary, behavioural and other environmental exposures, including physical and psychological stressors. The epigenome can be viewed as an important modifier of disease susceptibility, responsiveness to interventions and resilience to stressful circumstances. DNA methylation is the most widely studied epigenomic mark. Abnormalities in DNA methylation are associated with many diseases and manifest through inappropriate gene expression. Through comparative analysis of methylome data we can attain a clearer understanding of the molecular mechanisms that underlie pathology in different population subsets. Epigenomic profiling can provide informative biomarkers with potential for epigenomic reversibility and an attractive and potentially lucrative target for clinical intervention.

What is involved – describe the work, who you work with, where and how long it will take?

Along with my co-investigators: A/Prof Peter Larsen, Dr Ana Holley, Dr Scott Harding, this pilot study is on a subset of samples collected from patients from the Wellington Acute Coronary Syndrome (ACS) registry. The funds will be used to explore epigenomic differences between 17 Myocardial Infarction (MI) patients previously identified as ‘low risk’ who have had further cardiac events in the year following their index event with patients who have not had further cardiac events in the one year post initial event. This will focus on using RRBS (reduced representation bisulphite sequencing) to look at methylation differences between the two populations focusing on CpG islands (areas in the human genome likely to be associated with genes) in the genome from DNA already extracted from peripheral blood of ACS patients. It is hoped that this would identify biomarkers associated with differential pathology or recurrent cardiac events in these individuals. These biomarkers could potentially be used as predictors of disease/indicators of susceptibility/risk and aid in management and rehabilitation of young low risk individuals who have already presented with MI. We have already extracted DNA from blood samples and are awaiting the sequencing data. Once we have this I will be able to carry out the bioinformatic analysis of the sequencing data to explore methylation differences between the two groups. We hope to have preliminary data by August this year.

What is exciting you in what you are discovering?

DNA methylation response facilitates the identification of gene response to environmental stressors and could potentially contribute to aiding risk assessment and biomarker development for human studies. The potential application of epigenetic biomarkers in medicine is exciting as they offer the potential to identify and treat aberrant methylation patterns before the onset of disease symptoms.

What do you hope to achieve?

We hope to identify epigenomic biomarkers specific to the young patients presenting with MI.

What are your hopes beyond this research for the future of the study?

The potential application of epigenetic biomarkers in medicine is exciting as they offer the potential to identify and treat aberrant methylation patterns before the onset of disease symptoms. Future funding applications are likely to explore this further, maintain and grow connections both internally at UOW and externally with international collaborators. Follow on projects after this pilot study could also explore how to clinically address maladapted epigenomes and even explore the potential legacy effects of transmitted epigenomic imprints. This would have important implications in terms of how we assess heritability of disease; health equity and disease risk.

See all of the recipients of the 2017 second funding round here.

Interview with Michelle Thunders - identifying epigenomic biomarkers as potential predictors of disease or indicators of susceptibility in young MI patients

 
 
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