Sarcomere, Muscle physiology, Cardiomyopathy, Hypertrophy, Heart Failure

I am chair of the Department of Physiology at the Amsterdam University Medical Center.

My main research interest is the role of sarcomeric proteins in cardiac performance, both in health and disease. As mutations in sarcomeric proteins are a frequent cause of heart disease, research on inherited cardiomyopathies is a central research line in Amsterdam UMC. My team at the Physiology department collaborates with clinical geneticists, cardiologists, cardiac surgeons and experts in in vivo cardiac imaging, enabling translational studies from bench to the patient.

Our expertise includes functional studies at single cardiac muscle cell and multicellular level, and mitochondrial studies in patient samples obtained during cardiac surgery, and stem cell-derived  heart models. Our translational studies in human are complemented with studies in a cardiomyopathy mouse model. Recent collaboration with CytoCypher enables high-throughput studies in (stem cell-derived) cardiomyocytes (compound screening, effects of disease modifiers). Our current research projects aim to define the role of mitochondrial dysfunction in onset of cardiac disease, metabolic stress (obesity) as secondary disease hit, and protein homeostasis with a focus on the microtubular network. The research is funded by a VICI, ZonMW-Heart Foundation translational research grant (ENERGY trial), LeDucq foundation, and a DCVA consortium grant (Heart Foundation and Stichting Hartedroom; Dosis consortium; Double-Dose research program).

Within Amsterdam, we team up in Amsterdam 4R, with scientists from Vrije Universiteit and ACTA to promote reproducibility of animal-free research, adding a 4th R to the 3R principle of animal research: Reduction, Refinement, Replacement and Reproducibility.

Relevant links:

https://dcvalliance.nl/our-consortia/double-dose

https://cardiomyopathie-onderzoek.nl/

https://www.youtube.com/watch?v=U9Y4EarYQ98

https://cost-metaheart.eu/structure/action-participants/

https://hcmpatient.eu/about-us/

Ongoing research projects:

NWO VICI grant: Innovational Research. Sarcomere inefficiency at the heart of hypertrophic cardiomyopathy.

Hartedroom: Proteomic analyses in paediatric cardiomyopathy.

Innovation grant Amsterdam UMC. Proof-of-concept voor precision medicine in erfelijke (hart)spierziekten.

Consortium grant Netherlands Heart Foundation & Stichting Hartedroom. Double Dose of energy and efforts of the national Dosis consortium to design and test new diagnostic and treatment strategies for inherited cardiomyopathies. Coordinators: Jolanda van der Velden & Rudolf de Boer.

NWO Human models: Proof-of-Concept for a human heart model to test patient-specific therapy-responsiveness. Coordinator.

Bristol Myers Squibb grant. Effect of mavacamten on the myofilament-mitochondrial axis in HCM with and without sarcomere mutation. 

CARMA - Biomarker discovery in cardiomyopathies: Improve diagnosis & finding a biotarget. Netherlands Heart Foundation.