H. Llewelyn Roderick
B.Sc, Ph.D., Professor (Hoogleraar)
ORCID ID: 0000-0001-7065-3523
Curriculum Vitae (CV) - Contact - Open Lab Positions
Keywords: calcium, IP3, epigenetics, cardiac, hypertrophy
Research track: heart, cardiomyocyte
Epigenetics, Signalling and Cardiac Adaptation in Life and Ageing
Through delineating how cardiac myocytes as well as other cardiac cell types respond, interact and adapt over different timescales (ms to a lifetime) to developmental and environmental cues, including ageing, we aim to identify new biology and approaches for therapeutic intervention – this is the research ladder to a cure.
Our research is covered by three interlinked topics:
Excitation Contraction Coupling – control of dyadic Ca2+ signalling in health and disease.
Excitation Transcription Coupling – regulation of gene expression contributing to cardiac hypertrophy - a particular interest is the role of subcellular Ca2+ signals.
Cardiac Epigenetics – how epigenomic remodelling contributes to establishing and maintaining the phenotype/transciptome of individual cardiac cell types - during development, disease and ageing.
Heterocellular interactions - by single cell RNA and epigenomic analysis, we identify how intra- and inter cell heterogeneity alterations in disease contribute to functional and electrical remodelling.
Strategies:
Our research is multi-scale – spanning from molecule to myocyte to organ to organism. We employ rodent (including surgically and genetically modified) and highly relevant pig preclinical models as well as human patient samples and stem cells. Advanced animal and cell imaging combined with next generation sequencing tools including single nucleus RNA and epigenome analysis allow us to probe genome to (patho)physiology and through this identify new mechanisms and therapeutic targets
Why do we study cardiac remodelling?
Heart failure and cardiovascular diseases are a major cause of mortality and morbidity worldwide. HF is a terminal response to pathologies including myocardial infarction, aortic stenosis, prolonged hypertension, metabolic syndromes, cancer therapies and genetic factors. Age is also a significant risk factor for HF. Prior to HF, these pathologies induce cardiac remodelling, which is associated with hypertrophic growth of cardiac myocytes and phenotypic changes and alterations in abundance of the other cell types of the heart including fibroblasts, endothelial cells and immune cells. Given that transplant is the only therapy for HF, increasing our understanding of the mechanisms that bring about HF and associated pathologies or that can be modified to improve cardiac function or reverse pathology is key to improved cardiac health and the healthspan of the population.