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Toepfer Group: Cardiac Physiology and Disease Modeling

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.

Our team

DPhil Projects Available

Toepfer Group - Elucidating the role of disease modifying gene variants in inherited cardiomyopathies using induced pluripotent stem cell derived cardiomyocytes and CRISPR/Cas-9.

Selected publications

Funders:

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       Crest of the Royal Society.

Related research themes

We aim to better understand, diagnose and treat heart and vascular disease through our extensive cutting edge research programmes. We have a particular focus on understanding disease mechanisms and on new approaches to stratifying patients. Our expertise encompasses genetic studies to identify causative and risk genes, cardiovascular physiology and cellular biology to understand health and disease, the development and application of advanced imaging, experimental medicine and clinical trials.
Cardiovascular Science
Understanding the fundamental biology that drives embryonic development and tissue maintenance provides the basis of much of our research into blood diseases, the cardiovascular system and rare genetic conditions.
Stem Cells and Developmental Biology
Building on critical findings from our research streams, we are initiating new drug discovery programmes. Many of our researchers are engaged in target discovery and target validation research – elucidating molecular pathways that can be manipulated for disease modification.
Experimental Therapeutics
Employing a range of genetic techniques, we probe the fundamental causes of disease. Our expertise spans identification of causative genes in rare inherited diseases, through to elucidating complex gene regulatory pathways and exploration of susceptibility to common disease through genome-wide association studies. We use cutting edge techniques to manipulate the genome to determine how particular genes work and study how variants in regulatory DNA may contribute to common disease. An important overall aim is to improve the management of human genetic diseases.
Genetics, Genomics and Genome Biology
A raft of cellular and molecular biology techniques underpin much of the work we do to elucidate the mechanisms of disease. We use established techniques to answer new questions and also develop our own novel and unique methodologies to drive further innovation.
Cellular and Molecular Biology
We seek to bridge the ‘innovation gap’ between ‘basic’ research in the laboratory and tangible benefits for patients. Our researchers aim to develop novel approaches to treating disease and we have particular strengths in evaluating technologies such as antibody therapy and gene therapy, and using new techniques for target discovery. Many of our researchers collaborate with biotech and industry partners to accelerate progress along the drug discovery pipeline and assess these new treatments in the clinic.
Emerging Therapies and Drug Discovery