Brief summary of research over the last five years
The main research interest of the van der Velden group is to understand the role of sarcomeric proteins in cardiac performance for which we have designed several specific protein analyses and functional assays. Together with the physics department, we developed a method to measure force in intact cardiac muscle cells and at the same time measure changes in intracellular calcium (. This set-up is currently used by many other scientists, who are trained in the department for Physiology at the VU University Medical Center in Amsterdam. As mutations in sarcomeric proteins are a frequent cause of heart disease at young age, we initiated research on this topic in 2006. European and prestigious national grants enabled us to obtain a leading international position within cardiomyopathy research. The national CVON-consortium (DOSIS) funded by the Netherlands Heart Foundation aims to study genetic and environmental effects in cardiomyopathy development (https://www.hartstichting.nl/onderzoek/). The translational research projects help to build sufficient proof to initiate clinical trials to prevent disease at an early stage of cardiomyopathy.
Director of the Amsterdam Cardiovascular Sciences Network of VU University Medical Center (VUmc) & Amsterdam Medical Center (AMC) (together with Mat Daemen)(http://www.amsterdamresearch.org).
Chair of Physiology & Director of the CV Research Institute of VUmc (http://www.vumc.com/branch/physiology).
Netherlands Heart Institute Professor on Cardiomyopathies
Top 5 recent publications
Helmes M, Najafi A, Palmer BP, Breel E, Rijnveld N, Iannuzzi D, van der Velden J.
Mimicking the cardiac cycle in intact cardiomyocytes using diastolic and systolic force clamps; measuring power output.
Cardiovascular Research 2016; 111:66-73.
SequeiraV, Najafi A, Wijnker PJM, dos Remedios C, Michels M, Kuster DWD, van der Velden J.
ADP-stimulated contraction: a predictor of thin-filament activation in cardiac disease.
Proceedings of the National Academy of Sciences 2015;112:E7003-7012.
van der Velden J, Ho CY, Tardiff J, Olivotto I, Knollmann BC, Carrier L.
Research priorities in sarcomeric cardiomyopathies.
Cardiovascular Research 2015;105:449-556.
With editorial by G Hasenfuss. Sarcomeric cardiomyopathies: from bedside to bench and back.
Witjas-Paalberends ER, Güçlü A, Germans T, Knaapen P, Harms HJ, Vermeer AMC, Christiaans I, Wilde AAM, dos Remedios C, Lammertsma AA, van Rossum AC, Stienen GJM, van Slegtenhorst M, Schinkel AF, Michels M, Ho CY, Poggesi C, van der Velden J.
Gene-specific increase in energetic cost of contraction in hypertrophic cardiomyopathy caused by thick filament mutations.
Cardiovascular Research 2014; 103:248-57.
With editorial by JS Ingwall.The energetic cost of contraction is higher in the myocardium of patients with hypertrophic cardiomyopathy.
Sequeira V,* Wijnker PJM,* Nijenkamp LLAM, Kuster DWD, Najafi A, Witjas-Paalberends ER, Regan JA, Boontje NM, ten Cate FJ, Germans T, Carrier L, Sadayappan S, van Slegtenhorst MA, Zaremba R, Foster DB, Murphy AM, Poggesi C, dos Remedios C, Stienen GJM, Ho CY, Michels M, van der Velden J.
Perturbed length-dependent activation in human hypertrophic cardiomyopathy with missense sarcomeric gene mutations.
Circulation Research 2013;112:1491-505. *shared first author.
With editorial by S Huke and BC Knollmann. Familial hypertrophic cardiomyopathy: Is the Frank-Starling Law kaput?
Selection of ongoing projects
- Cardiovasculair Onderzoek Nederland (CVON) research grant. Determinants of susceptibility in inherited cardiomyopathy: towards novel therapeutic approaches. Acronym: Dosis. Coordinators: Jolanda van der Velden & Rudolf de Boer (UMCG). National consortium grant.
- NIH (National Institutes of Health) Research grant – National Heart, Lung and Blood Institute. ‘Molecular physiology of troponin I variants.’ Collaboration with Prof Anne Murphy (Johns Hopkins University School of Medicine, Baltimore, USA).
- Hartstichting/stichting Hartedroom: Co-PI on ‘Boosting chaperone networks to counteract juvenile DCM caused by chaperone mutations.’ Harrie Kampinga & Bianca Brundel (UMCG).
- Rembrandt Research grant. Functional genomics to identify the pathomechanisms of human dilated cardiomyopathy caused by mutations in the giant sarcomeric protein titin. Collaboration with Yigal Pinto (AMC) (PhD project).
- Cardiovasculair Onderzoek Nederland (CVON) research grant. Approaching heart failure by translational research of RNA mechanism (ARENA). Principal investigator and work package leader. National collaboration: coordinators: Prof dr. Y Pinto & Prof dr. L de Windt.