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.
Blanca Rodriguez (Computer Science, Oxford)
Alfonso Bueno-Orovio (Computer Science, Oxford)
Manuela Zaccolo (DPAG, Oxford)
Christine Seidman (Harvard Medical School)
Jonathan Seidman (Harvard Medical School)
Christopher Chen (Boston University)
Nerea Lasarte (Grousbeck Gene Therapy Center, Harvard)
IN THE PRESS AND EDITORIALS
- BBC website 'Cancer treatment broke my heart, but I've survived'
- Nature Reviews Cardiology Editorial ‘Modulating myosin function to treat hypertrophic cardiomyopathy’
- Circulation Editorial ‘Manipulating Myosin May Help Treat Hypertrophic Cardiomyopathy’
- Circulation Research Editorial ‘High-Throughput Contractility Assay for Human Stem Cell-Derived Cardiomyocytes: One Beat Closer to Tracking Heart Muscle Dynamics’
- HMS press release and interview ‘On the Beat’
- HMS press release and interview ‘Bad Brakes’
- HMS press release and interview 'Revving the engine'