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Understanding key mechanisms that govern cardiac muscle function in health and disease

Our group is interested in uncovering and understanding key mechanisms of disease that affect cardiac muscle function. We have a particular interest in understanding how regulation of cardiac muscle contraction is altered in common acquired and inherited cardiovascular diseases.

We do this by using cutting edge techniques in cellular imaging, employing human induced pluripotent stem cell derived cardiomyocytes (iPSC-CMs), and CRISPR/Cas-9 to understand human cardiovascular disease in the dish.

 We have two key focuses in the lab:

1) Understanding how inherited heart conditions including hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) alter cardiomyocyte function. We do this by using CRISPR Cas-9 genome engineering in combination with iPSC-CMs to screen how HCM and DCM causing variants cause disease. We can then use these systems to screen novel therapeutics in the dish. We have designed multiple techniques to make these analyses feasible and rapidly deployable: SarcTrack and CalTrack.

2) Investigate the processes that alter cardiac muscle function in acquired cardiac diseases including myocardial infarction, atrial fibrillation, and heart failure. We are able to use biochemical techniques twinned with fluorescent imaging to assess how cardiac myosin states are altered in disease tissues. This technology allows us to uncover key disease mechanisms that alter heart muscle function, allowing insight into these common heart muscle diseases. 

We have multiple key collaborations within the University of Oxford and internationally. Together we focus on pushing the boundaries of understanding in acquired and inherited cardiovascular disorders of the heart muscle.

 

DPhil Project Available: 

2026 Toepfer Group: Elucidating the role of disease modifying gene variants in inherited cardiomyopathies using induced pluripotent stem cell derived cardiomyocytes and CRISPR/Cas-9 — Radcliffe Department of Medicine

Our team

Selected publications

Targeted genetic therapies for inherited disorders that affect both cardiac and skeletal muscle.

Journal article

Psaras Y. and Toepfer CN., (2024), Exp Physiol, 109, 175 - 189

CalTrack: High-Throughput Automated Calcium Transient Analysis in Cardiomyocytes.

Journal article

Psaras Y. et al, (2021), Circ Res, 129, 326 - 341

SarcTrack.

Journal article

Toepfer CN. et al, (2019), Circ Res, 124, 1172 - 1183

Hypertrophic cardiomyopathy mutations in MYBPC3 dysregulate myosin.

Journal article

Toepfer CN. et al, (2019), Sci Transl Med, 11

CRISPR/Cas9-Mediated Fluorescent Tagging of Endogenous Proteins in Human Pluripotent Stem Cells.

Journal article

Sharma A. et al, (2018), Curr Protoc Hum Genet, 96, 21.11.1 - 21.11.20

post-MI power struggle: adaptations in cardiac power occur at the sarcomere level alongside MyBP-C and RLC phosphorylation.

Journal article

Toepfer CN. et al, (2016), Am J Physiol Heart Circ Physiol, 311, H465 - H475

Myosin Regulatory Light Chain (RLC) Phosphorylation Change as a Modulator of Cardiac Muscle Contraction in Disease

Conference paper

Toepfer C. et al, (2013), BIOPHYSICAL JOURNAL, 104, 309A - 310A