DrAndreia Bernardo

Left ventricle development – we combine human pluripotent stem cells and mouse models to understand how left ventricle cardiomyocytes are specified and elucidate the gene regulatory networks orchestrating these cell fate decisions. We are using RNA-sequencing and bioinformatics tools to identify the key transcription factors and molecular and functional analysis tools to explore their function. These studies provide both mechanistic answers and will inform strategies to streamline the generation of patient specific left ventricle cardiomyocytes using direct reprogramming bypassing the need to reprogramme cells back to a pluripotent state first in order to use them in precision medicine to study left ventricle disease.

Left ventricle maturation – pluripotent stem cell derived cardiomyocytes are known for their immaturity. Our left ventricle cardiomyocytes, despite more mature than those generated using the standard protocol, retain some immature features. Using bioinformatics tools we have determined what our cells are missing in comparison to adult human left ventricle cardiomyocytes and we are now exploring how best to utilise this information to understand the process of maturation and develop new methods to address this in vitro maturity challenge and improve faithfulness of our cell model for disease modelling, drug discovery and cardiotoxicity assays.

Left ventricle ageing – ageing heart health is a particular area of concern, especially since the heart has little to no regenerative capacity. We have developed an isogenic wild type human pluripotent cell line from a progeria (premature ageing) cell line to model progeria syndrome and perform comparisons using cell lines with the same genetic background. We are also determining if these cells can be used a model of premature left ventricle ageing.

Left ventricle disease – we have collaborations set up to model various heart diseases using our cell models, namely hypertrophic cardiomyopathy, progeria syndrome and down syndrome. We are particularly interested in the effects of inflammation on left ventricle health and disease.