Diederik Kuster

Assistant Professor

Research interests

My research has focused on understanding molecular changes that underlie contraction and relaxation in the context of hypertrophic cardiomyopathy. As a PhD student, I studied changes in transcription factors that drive physiological and pathological hypertrophy in swine. After that I switched to the department of Physiology as a postdoc to focus on the function of cardiac myosin binding protein C (cMyBP-C). From 2012-2014, I worked in Dr Sadayappan’s laboratory at Loyola University Chicago. I worked on using cMyBP-C as a biomarker, and on the disease mechanism of the most common HCM-associated MYBPC3^Δ25bp mutation.

My current research focuses on molecular changes in HCM patient samples and models of the disease. Combining biochemical and biophysical techniques with in vivo and in vitro measurements of cardiac/cardiomyocyte function, I aim to elucidate the still elusive HCM pathophysiology.

Key publications

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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. Circ Res. 2023 133(5):387-399.
Schuldt M, Pei J, Harakalova M, Dorsch LM, Schlossarek S, Mokry M, Knol JC, Pham TV, Schelfhorst T, Piersma SR, Dos Remedios C, Dalinghaus M, Michels M, Asselbergs FW, Moutin MJ, Carrier L, Jimenez CR, van der Velden J*, Kuster DWD*. Proteomic and Functional Studies Reveal Detyrosinated Tubulin as Treatment Target in Sarcomere Mutation-Induced Hypertrophic Cardiomyopathy. Circ Heart Fail. 2021 14(1):e007022.
Hilderink S, Schuldt M, Goebel M, Jansen VJ, Manders E, Moorman S, Dorsch LM, van Steenbeek FG, van der Velden J, Kuster DWD. Characterization of heterozygous and homozygous mouse models with the most common hypertrophic cardiomyopathy mutation MYBPC3c.2373InsG in the Netherlands.
Kuster DW, Govindan S, Springer TI, Martin JL, Finley NL, Sadayappan S. A hypertrophic cardiomyopathy-associated MYBPC3 mutation common in populations of South Asian descent causes contractile dysfunction. J Biol Chem. 2015 290:5855-67. J Mol Cell Cardiol. 2023 185:65-76.
Kuster DW, Sequeira V, Najafi A, Boontje NM, Wijnker PJ, Witjas-Paalberends ER, Marston SB, dos Remedios CG, Carrier L, Demmers JA, Redwood CS, Sadayappan S, van der Velden J. GSK3β phosphorylates newly identified site in the Pro-Ala rich region of cardiac myosin binding protein C and alters cross-bridge cycling kinetics in human. Circ Res 2013 112:633-9

Ongoing research projects:

HEARTDISC (2024-2028, Hartstichting): Understanding the mechano-signalling role of the Z-disc in the pathogenesis of Hypertrophic Cardiomyopathy. Collaborative grant together with Katja Gehmlich (University of Birmingham) and Claudia Crocini (Charité Berlin).
CADENCE (2024-2028, Health~Holland): Taming cell-to-cell variability in drug response to improve cardiac relaxation. Build a new setup to enable single cell perfusion. This will allow us to measure cell-to-cell variability in drug response and their underlying mechanism. Collaboration with Ionoptix and Fluicell (Sweden).
ProAngio HCM (2024-2026, DCVA): Pro-angiogenic gene therapy for hypertrophic cardiomyopathy. Use pro-angiogenic gene therapy approaches to improve function in HCM. Collaboration with Monika Gladka (Amsterdam UMC)
DOUBLE-DOSE (2021-2026, Hartstichting): Double Dose of energy and efforts of the national DOSIS consortium. The role of metabolic stress and obesity on cardiomyopathy pathophysiology
Leducq Cytoskeleton Network (2021-2026, Leducq Foundation): Cytoskeletal regulation of cardiomyocyte homeostasis in health and disease. Leducq consortium on microtubule changes in heart failure and cardiomyopathies.

Group members

Co-promotor of the following PhD students:

Sıla Algül
Inez Duursma
Sarah Hilderink
Floor van den Dolder
Ali Nassar
Vincent Warnaar
Ilse Altenburg
Eslem Yürümez

Technicians

Daan Hoomoedt
Valentijn Jansen
Remco Hoogervorst

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