| Title: | Exploring mechanisms of cardiovascular disease associated with diabetes |
| Lead Institution: | University of Leeds |
| Principal investigator: |
Application 528243
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About
This application is for a PhD project that seeks to understand the molecular basis of cardiovascular disease in people with diabetes. Diabetes Mellitus is associated with a high risk of cardiovascular complications arising from arterial disease e.g. myocardial infarction, stroke, heart failure, limb ischaemia. Even individuals with well managed diabetes are at higher risk of many of these complications, which highlights a need for novel therapies guided by understanding of the underpinning molecular mechanisms, ideally targeted by linked biomarkers. RNA-seq and other 'omics technologies can be used to investigate how diabetes alters gene, protein and metabolite expression in an unbiased way. Our analysis of in house and publicly available data has established molecular hits that are differentially expressed in vascular tissues in the context of diabetes. However, to be confident in these, and to better understand their relevance to organ dysfunction, we need to validate them. Whilst this can be conducted using the same technologies in a new cohort, often this is not practical due to the very large expense. Moreover, validation using an orthogonal technology can add further confidence in identified hits. Therefore, we intend to use the UK Biobank plasma proteomics, metabolomics and genetics data (as eQTLs and pQTLs) to define the association between molecular hits (from other cohorts) and participant phenotype, comparing people with versus without diabetes. This will allow us to validate differential expression signatures and, for those that are confirmed, define how they are associated with relevant disease events (e.g. incident myocardial infarction). We will also explore associations between molecular expression and markers of diabetes (such as HbA1c, duration, complications) or obesity (e.g. BMI) severity. This may help us to establish novel biomarkers of diabetes-associated cardiovascular disease and improve understanding of novel therapeutic targets.1 Publication
| Pub ID | Title | Author(s) | Year | Journal |
|---|---|---|---|---|
| 21446 | Analysis of the diabetic arterial transcriptome to define novel biomarkers of macrovascular disease | Aya Shouma (+12) | 2026 | Diabetes and Vascular Disease Research |
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