Jolanda van der Velden
email: j.vandervelden1@amsterdamumc.nl | orchid: https://orcid.org/0000-0001-5224-5788
Research Interests
A main research interest of the van der Velden team is the role of sarcomeric proteins in cardiac performance. As mutations in sarcomeric proteins are a frequent cause of heart disease, research on inherited cardiomyopathies is a central research line in Amsterdam, and experiments are performed from bench to the clinic. 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. Close collaboration with clinical departments allows translational research in which the functional studies in cardiac samples are combined with in vivo parameters of cardiac pump function and energetics. Her love for the cardiac sarcomere started during her PhD training, during which she initiated studies in single membrane-permeabilized cardiomyocytes isolated from human cardiac biopsies. Together with her PhD supervisor, Ger Stienen, after a training in the lab of Rick Moss, she was able to start studies on the human sarcomere in health and disease, and link the sarcomere proteome with myofilament function. A key finding was the increased cardiomyocyte passive force development in the heart of patients with preserved ejection fraction, which explains part of the impaired cardiac relaxation in these patients, and is caused by altered titin phosphorylation. Several main results in human hypertrophic cardiomyopathy are the haploinsuifficiency caused by truncation MYBPC3 mutations, blunted mutation-mediated length-dependence of force development, altered tubulin signature, and more recently pertubations in mitochondrial function. Overall, studies have shown mutation- and genotype-specific changes in cardiac function, which may ultimately improve patient-specific treatment.
Recent publications
- Wijnker PJM, Dinani R, van der Laan NC, Algül S, Knollmann BC, Verkerk AO, Remme CA, Zuurbier CJ, Kuster DWD, van der Velden J. Hypertrophic cardiomyopathy dysfunction mimicked in human engineered heart tissue and improved by SGLT2 inhibitors. Cardiovascular Research 2024:cvae004. doi: 10.1093/cvr/cvae004. Online ahead of print.
- Algül S*, Dorsch LM*, Sorop O, Vink A, Michels M, dos Remedios CG, Dalinghaus M, Merkus D, Duncker DJ, Kuster DWD, van der Velden J. The microtubule signature in cardiac disease: etiology, disease stage and age dependency. J Comp Physiol B 2023;193:581-595. doi: 10.1007/s00360-023-01509-1. *shared first authorship.
- Algül S*, Schuldt M*, Manders E, Jansen V, Schlossarek S, de Goeij-de Haas R, Henneman AA, Piersma SR, Jimenez CR, Michels M, Carrier L, Helmes M, van der Velden J, Kuster DWD. EGFR/IGF1R signaling modulates relaxation in hypertrophic cardiomyopathy. Circulation Research 2023;133:387-399. doi: 10.1161/CIRCRESAHA.122.322133.*shared first authorship.
- Dinani R, Manders E, Helmes M, Wang L, Knollmann B, Kuster DWD, van der Velden J. Real-Time measurements of calcium and contractility parameters in human induced pluripotent stem cell-rerived cardiomyocytes. JoVE: Journal of Visualized Experiments 2023; 195. doi: 3791/65326. Video: https://www.jove.com/v/65326
- Pioner JM, Vitale G, Steczina S, Langione M, Margara F, Santini L, Giardini F, Lazzeri E, Piroddi N, Scellini B, Palandri C, Schuldt M, Spinelli V, Girolami F, Mazzarotto F, van der Velden J, Cerbai E, Tesi C, Olivotto I, Bueno-Orovio A, Sacconi L, Coppini R, Ferrantini C, Regnier M, Poggesi C. Slower calcium handling balances faster crossbridge cycling in human MYBPC3 Circulation Research 2023;132:628-644. doi: 10.1161/CIRCRESAHA.122.321956.
- Nollet EE, Duursma I, Rozenbaum A, Eggelbusch M, Wüst RCI, Schoonvelde SAC, Michels M, Jansen M, van der Wel NN, Bedi KC, Margulies KB, Nirschl J, Kuster DWD, van der Velden J. Mitochondrial dysfunction in human hypertrophic cardiomyopathy is linked to cardiomyocyte architecture disruption and corrected by improving NADH-driven mitochondrial respiration. European Heart Journal 2023; 44:1170-1185. doi:1093/eurheartj/ehad028.
- van der Velden J, et al. Animal models and animal-free innovations for cardiovascular research: current status and routes to be explored. Consensus document of the ESC working group on myocardial function and the ESC Working Group on Cellular Biology of the Heart. Cardiovascular Research 2022;118:3016-3051. doi:10.1093/cvr/cvab370.
- Schuldt M, Pei J, Harakalova M, Dorsch LM, Schlossarek S, Mokry M, PhD, Knol JC, Pham TV, Schelfhorst T, Piersma SR, dos Remedios C, Dalinghaus M, Michels M, Asselbergs FW, Moutin MJ, Carrier L, Jimenez CJ, van der Velden J,* Kuster DWD.* Proteomic and functional studies reveal detyrosinated tubulin as treatment target in sarcomere mutation-induced hypertrophic cardiomyopathy. *shared last author. Circulation: Heart Failure 2021; doi:10.1161/CIRCHEARTFAILURE.120.007022. Editorial: Margulies KB, Prosser BL. Tubulin detyrosination: an emerging therapeutic target in hypertrophic cardiomyopathy.
- Schuldt M, Johnston JR, He H, Huurman R, Pei Y, Harakalova M, Poggesi C, Michels M, Kuster DWD, Pinto JR, van der Velden J. Mutation location of HCM-causing troponin T mutations defines the degree of myofilament dysfunction in human cardiomyocytes. Journal of Molecular and Cellular Cardiology 2021;150:77-90.
- Parbhudayal RY, Harms HJ, Michels M, van Rossum AC, Germans T, van der Velden J. Increased myocardial oxygen consumption precedes contractile dysfunction in hypertrophic cardiomyopathy caused by pathogenic TNNT2 gene variants. Journal of the American Heart Association 2020;9:e015316. doi:10.1161/JAHA.119.015316.
Ongoing research projects
| Applicant | Total amount | Own group | Year of award | |
| ZonMW Open competition. Human heart-mimetic models for personalized medicine (HEARTTWIN) – together with Robert Passier (UTwente) | €750,000 | €375,000 | 2024 | |
| CARMA – Biomarker discovery in cardiomyopathies: Improve diagnosis & finding a biotarget (Double Dose consortium) | €2,218,000 | €390,000 | 2022 | |
| Bristol Myers Squibb grant. Effect of mavacamten on the myofilament-mitochondrial axis in HCM with and without sarcomere mutation. | €225,200 | €225,200 | 2021 | |
| NWO Human models: Proof-of-Concept for a human heart model to test patient-specific therapy-responsiveness. Coordinator. | €860,000 | €700,000 | 2021 | |
| 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 | €3 million | €624,000 | 2021 | |
| NWO VICI grant: Innovational Research. Sarcomere inefficiency at the heart of hypertrophic cardiomyopathy. | €1,500,000 | €1,500,000 | 2018 | |
| Co-applicant | ||||
| EUropean network to tackle METAbolic alterations in HEART failure – EU-METAHEART | COST network: European Coorperation in Science and Technology | 2023 | ||
| Fondation Leducq Transatlantic Network of Excellence. Cytoskeletal regulation of cardiomyocyte homeostasis in health and disease. Principal Investigator | €6 million
|
€720,000 | 2020 | |
Group members
Promotor PhD projects
- Unload the ventricle: Unmasking the regenerative capacity of the heart. Rembrandt grant Jan Willem Buikema & Jesper Hjortnaes. Student: Luuk Kemna (2024-2027)
- Mechanically-induced nuclear abnormalities as a disease driver of HCM. Netherlands Heart Foundation Dekker grant Tyler Kirby. Student: Linda Micali (2024-2027)
- Stem cell models for tailoring patient-specific heart failure treatment (CRISTAL) – Netherlands Heart Foundation Dekker grant Jan Willem Buikema. Student: Devin Verbueken (2022-2026)
- Cardiac and skeletal muscle pathomechanisms in KBTBD13-mediated disease. VENI grant Josine de Winter. Student: Rianne Baelde (2022-2026)
- VICI & CARMA. Student: Julia Visch (2022-2026)
- VICI & BMS project. Student: Vincent Warnaar (2022-2026)
- Proper Therapy grant. Students: Adriana Passadouro (2022-2026) & Ali Nassar (2021-2025)
- LeDucq program microtubules. Students: Sila Algul (2021-2025) & Inez Duursma (2021-2025)
- DCVA Double Dose. Students: Floor van den Dolder (2021-2025), Sarah Hilderink (2021-2025) & Talitha Spanjersberg (2021-2025)
- Senior Dekker grant Kakkhee Yeung: The key role of smooth muscle cell function in aortic aneurysms. Student: Karlijn Rombouts (2020-2024)
- VICI project. Student: Rafeeh Soleimanidinani (PhD in 2024)
- ENERGY trial. Beau van Driel (PhD in 2024)
- VICI project & Chinese scholarship. Unlocking the molecular clues for cardiomyocyte proliferation. Qianliang Yuan. April 2024.
post-doc:
- Edgar Nollet
Media
AD VALVAS: De minihartjes van Jolanda van der Velden kloppen écht
YouTube: Human heart models to reduce animal studies | Transition animal-free innovations Amsterdam