Jolanda van der Velden
RESEARCH INTEREST
The main focus of the research involves investigation of changes in cellular protein composition and function, which contribute to impaired cardiac muscle cell function in heart failure, and may be target for drug therapy. The research is characterized by a multi-disciplinary approach with strong interaction between fundamental and clinical research. We combine multiple functional cell assays with cardiac imaging in patient groups. More recently, we initiated studies on mitochondrial dysfunction and derailment of the protein quality control system in cardiac disease.
Two main research lines:
Failure of the heart muscle caused by mutations in sarcomeric proteins in inherited cardiomyopathies.
Diastolic dysfunction in cardiac disease.
KEY PUBLICATIONS
Güçlü A, Knaapen P, Harms HJ, Parbhudayal RY, Michels M, Lammertsma AA , van Rossum AC, Germans T, van der Velden J. Disease stage-dependent changes in cardiac contractile performance and oxygen utilization underlie reduced myocardial efficiency in human inherited hypertrophic cardiomyopathy. Circulation Cardiovascular Imaging 2017, in press.
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.
Najafi A, Sequeira V, Helmes M, Bollen IAE, Goebel M, Regan JA, Lucie Carrier L, Diederik WD Kuster DWD, van der Velden J. Selective phosphorylation of PKA targets after β-adrenergic receptor stimulation impairs myofilament function in Mybpc3-targeted HCM mouse model. Cardiovascular Research 2016;110:200-14.
Wijnker PJM, Friedrich FW, Dutsch A, Reischmann S, Eder A, Vollert-Mannhardt I, Mearini G, Eschenhagen T, van der Velden J, Carrier Comparison of the effects of a truncating and a missense MYBPC3 mutations on contractile parameters of engineered heart tissue. Journal of Molecular and Cellular Cardiology 2016; 97:82-92.
Sequeira V, 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. WCN (Werkgroep Cardiologische Centra Nederland) onderzoeksprijs 2015/2016.
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
ONGOING RESEARCH PROJECTS
2017-2020 Program translational research (ZonMW-Hartstichting) grant 2017. Extra energy for hearts with a genetic defect: ENERGY trial. Coordinator: Jolanda van der Velden; collaboration with Michelle Michels (Erasmus MC).
2015-2020 Cardiovasculair Onderzoek Nederland (CVON) research grant 2015. Determinants of susceptibility in inherited cardiomyopathy: towards novel therapeutic approaches. Acronym: Dosis. Coordinators: Jolanda van der Velden, Bianca Brundel (VUmc) & Rudolf de Boer (UMCG). National consortium grant (VUmc, AMC, UMCG, UMCU, Erasmus MC).
2015-2018 NIH (National Institutes of Health) Research grant – National Heart, Lung and Blood Institute. ‘Molecular physiology of troponin I variants.’ Collaboration with Prof dr. AM Murphy (Johns Hopkins University School of Medicine, Baltimore, USA).
2014-2016 Hartstichting/stichting Hartedroom 2013: Co-PI on ‘Boosting chaperone networks to counteract juvenile DCM caused by chaperone mutations.’ Collaboration with Harrie Kampinga & Bianca Brundel (UMCG).
2013-2017 Rembrandt Research grant 2013. Functional genomics to identify the pathomechanisms of human dilated cardiomyopathy caused by mutations in the giant sarcomeric protein titin. Collaboration with Yigal Pinto (AMC).
2012-2017 Cardiovasculair Onderzoek Nederland (CVON) research grant 2011. Approaching heart failure by translational research of RNA mechanism (ARENA). Principal investigator and work package leader. National collaboration: coordinators: Yigal Pinto & Leon de Windt.
GROUP MEMBERS
Post-docs
Elza van Deel (ICaR-VU grant)
Paul Wijnker (NIH funding)
Vasco Sequiera (ACS post-doc grant, SERVIER-ISHR research award)
PhD students
Ahmed Güçlü (VIDI, HS, PhD May 18 2017)
Aref Najafi (CVON-ARENA)
Louise Nijenkamp (CVON-ARENA)
Ilse Bollen (Rembrandt grant)
Rahana Parbhudayal (VIDI, ZonMW-HS)
Maike Schuldt (CVON-DOSIS)
Larissa Dorsch (CVON-DOSIS)