Violetta Steeples

My research is focussed upon understanding the molecular mechanisms underlying hypertrophic cardiomyopathy and ultimately aims to use this knowledge to investigate potential cures. Hypertrophic cardiomyopathy is often associated with the presence of a genetic variants. These variants are most commonly found in genes encoding proteins with important structural roles in heart cells (cardiomyocytes), but also in genes with other roles such as regulating energy production and signalling within the cell and even in genes with, as yet undefined roles.

I introduce the genetic variants found in patients with hypertrophic cardiomyopathy into induced pluripotent stem cells (iPSCs) with CRISPR-Cas9 genome editing. Then I use small molecules to direct differentiation of these iPSCs into cardiomyocytes. I observe any physiological (e.g. beating strength) or biochemical (e.g. protein expression) differences between cardiomyocytes with and without the genetic variant of interest and investigate whether therapies can reverse these biological changes.

Publications

1. Metabolic profiling of aortic stenosis and hypertrophic cardiomyopathy identifies mechanistic contrasts in substrate utilization. Pal N et al. (2024). FASEB Journal

2. Comparing the effects of chemical Ca2+ dyes and R-GECO on contractility and Ca2+ transients in adult and human iPSC cardiomyocytes. Robinson P et al. (2023). Journal of Molecular and Cellular Cardiology

3. Impact of spliceosome mutations on RNA splicing in myelodysplasia: dysregulated genes/pathways and clinical associations. Pellagatti A, Armstrong RN, Steeples V et al. (2018). Blood

4. The U2AF1S34F mutation induces lineage-specific splicing alterations in myelodysplastic syndromes. Yip BH et al. (2017) Journal of Clinical Investigation

5. Chronic Activation of γ2 AMPK Induces Obesity and Reduces β Cell Function. Yavari A et al. (2016) Cell Metabolism