Tyler Kirby

Research focus:

Nuclear mechanotransduction in skeletal muscle adaptation and aging

Skeletal muscle has the remarkable ability to adapt to mechanical forces – when we do resistance training our muscles get bigger (hypertrophy), but when we age and reduce our activity, they get smaller (atrophy). While there is clear evidence supporting mechanotransduction pathways that stimulate protein synthesis as being central regulators of muscle mass, there are likely additional mechano-sensitive mechanisms important for controlling functional muscle adaptation.

Our lab is focused on understanding the cellular mechanisms that control muscle adaptation, with a specific focus on the cell nucleus. Previously, it was thought that the nucleus was just a passive organelle, simply responsible for housing our genetic material (DNA). However, in recent years it has been shown that the nucleus can directly respond to mechanical forces, a process termed ‘nuclear mechanotransduction’. The importance of nuclear mechanotransduction in cellular function is evident by the various genetic diseases that arise from mutations in proteins crucial to the transduction cascade. Intriguingly, these diseases preferentially affect cardiac and skeletal muscle, suggesting that nuclear mechanotransduction is critically important for striated muscle homeostasis. Our research integrates cell biology, bioengineering and whole-animal physiology approaches to study the role that nuclear mechanotransduction plays in skeletal muscle adaptation and aging.

Funded Projects

2019 – 2022 – Career Development Grant, The Muscular Dystrophy Association – DNA-PK hyperactivation in the progression of Emery-Dreifuss muscular dystrophy.

 

Key Publications

 

Kirby, T.J.*, A.J. Earle*, G.R. Fedorchak*, P. Isermann, J. Patel, S. Iruvanti, S.A. Moore, G. Bonne, L.L. Wallrath and J. Lammerding. Mutant lamins cause mechanically-induced nuclear envelope rupture and DNA damage in skeletal muscle cells. Nature Materials, 19 (4): 464-473, 2020. PMID: 31844279

 

Kirby, T.J.*, C.S Fry*, K. Kosmac, J. J. McCarthy, and C. A. Peterson. Myogenic progenitor cells control extracellular matrix production by fibroblasts during skeletal muscle hypertrophy. Cell Stem Cell, 20(1): 56-69, 2017. PMID: 27840022.

 

Kirby, T.J., R.M. Patel, T. M. McClintock, E. E. Dupont-Versteegden, C. A. Peterson, and J. J. McCarthy. Modulation of global transcriptional output within myogenic cells during hypertrophic growth. Molecular Biology of the Cell, 27(5): 788-798, 2016. PMID: 26764089

 

Kirby, T.J., J.D. Lee, J.H. England, T. Chaillou, K.A. Esser and J.J. McCarthy. Blunted hypertrophic response in aged skeletal muscle is associated with decreased ribosome biogenesis. Journal of Applied Physiology, 119(4): 321-327, 2015. PMID: 26048973

 

Fry, C.S., J.D. Lee, J. Mula, T.J. Kirby, J.R. Jackson, F. Liu., L. Yang, C.L. Mendias, E. E. Dupont-Versteegden, J. J. McCarthy, and C. A. Peterson. Inducible depletion of satellite cells in adult, sedentary mice impairs muscle regenerative capacity without affecting sarcopenia. Nature Medicine. 21(1): 76-80, 2015. PMID: 25501907.

* Indicates co-first authorship

 

 

Reinier Boon

Research focus

Ageing of the cardiovascular system.

Since 2016 Reinier Boon is an associate professor at the VU University Medical Center in Amsterdam and a W2 professor at the Goethe University in Frankfurt. Reinier received his PhD degree with honors in 2008 from the Academic Medical Center of the University of Amsterdam. He then started his post-doctoral work in the Institute for Cardiovascular Regeneration in Frankfurt, Germany in the laboratory of Prof. Dimmeler funded by the Netherlands organization for scientific research (NWO). He received multiple awards for his work on the effects of shear stress on endothelial cells and the role of microRNAs in aging of the cardiovascular system, including the prestigious Melvin L Marcus Award from the American Heart Association in 2010 and the Franz-Maximilian Groedel Research Prize of the German Cardiac Society in 2014. Research in his group is funded by the German Center for Cardiovascular Research (DZHK), the German research foundation (DFG), the European Research Council (Starting grant), Amsterdam Academic Alliance and the Dutch Scientific Organization NWO (Vidi).

The main focus of the research in the lab is ageing of the cardiovascular system. This is the main risk factor for cardiovascular disease and we are interested in the role of so-called non-coding RNA in this process. Current focus lies on long non-coding RNAs (lncRNAs), which control key cellular processes in endothelial cells and cardiomyocytes. We study lncRNAs in these cells that are (dys)regulated during ageing and aim to identify targets for therapeutic intervention. Our studies include functional in vitro and in vivo models, as well as molecular biology and biochemical assays.

Recent publications

Link: Research portal VUmc

Ongoing research projects

(2017-2020) Rembrandt Research Award (Rembrandt Institute): ‘14q32 non-coding RNAs in vascular disease’, Co-PI: Yael Nossent (LUMC).

(2017-2021) Vidi Grant from the Dutch Scientific Organization (NWO): ‘Non-coding RNA in cardiac ageing’.

(2016-2018) Amsterdam Academic Alliance Fellowship

2015-2019     ERC Starting Grant, ‘Non-coding RNA in vascular ageing’ (NOVA)

2014-2017     Collaborative Research Center SFB834: ‘Long non-coding RNAs as regulators of endothelial cell function’, Coordinated by Ingrid Fleming & Stefanie Dimmeler (Frankfurt).

 

Group members
Post-docs
Noelia Lozano-Vidal (Vidi grant)
Diewertje Bink (AAA grant)

PhD students
Laura Stanicek (Vidi grant)
Tan Phat Pham (AAA grant)
Veerle Kremer (Rembrandt grant)
Frankfurt: Patrick Hofmann (SFB834)
Frankfurt: Julia Trembinski (ERC)

Ger Stienen

Research focus

Origin of the alterations in contractile properties and energy utilisation by the mitochondria of cardiac muscle cells during heart failure; origin of skeletal muscle weakness resulting from alteration in cytoskeletal muscle proteins.

Ger Stienen received his MS degree in Experimental Physics at the Radboud University in Nijmegen in 1975. In 1981 he received his PhD degree in Physiology and worked from 1975 until 1985 as Research fellow/postdoc at the Department of Physiology of the University of Amsterdam (UvA). In 1985 he became staff member at the Laboratory for Physiology at VU University Medical Center in Amsterdam. Since 2006 he is Professor in Medical Physiology at VUmc/VU. He is Visiting Professor at the Institute of Biomedical Research, Manchester Metropolitan University in Manchester (UK) and at the Department of Human Anatomy and Physiology of the University of Padua (Italy). From 2009 until 2013 he has been Programme director of the Cardiovascular Research Master of VUmc.

Other Experience and Professional Memberships: 1996-2004 Chairman European Society for Muscle Research; 2004- Treasurer European Society for Muscle Research; 1997-2004 Editor Journal of Physiology; Organiser and Chairman of Sessions of various International Conferences.

Member of: Nederlandse Fysiologen Vereniging; Physiological Society, UK; Nederlandse Vereniging voor Biofysica; Biophysical Society, USA; European Society for Muscle Research; American Heart Association; European Society for Cardiovascular Research.

Honors and Awards: 2005 Member external evaluation committee Department of Human Anatomy and Physiology, University of Padua, Italy; 2007 Secretary external evaluation committee Institute for Fundamental and Clinical Movement Studies; 2013 Honorary doctorate University of Debrecen, Hungary.

 


 

Selection of recent publications

 

Wüst RCI, M Helmes and GJM Stienen (2015). Rapid changes in NADH and flavin autofluorescence in rat cardiac trabeculae reveal large mitochondrial complex II reserve capacity. Journal of Physiology 593(8): 1829-40.

Canato M, Scorzeto M, Giacomello M, Protasi F, Reggiani C, Stienen GJM. Massive alterations of SR free calcium in skeletal muscle fibers lacking calsequestrin revealed by a genetically encoded probe. Proc Natl Acad Sc USA 107: 22326-22331, 2010.

Scorzeto M, Giacomello M, Toniolo L, Canato M, Blaauw, B, Paolini C, Protasi, Reggiani C, Stienen GJM. Mitochondrial Ca2+-handling in fast skeletal muscle fibers from wild type and calsequestrin-null mice. Plos One 8(10):e74919, 2013.

de Man FS, van Hees HW, Handoko ML, Niessen HW, Schalij I, Humbert M, Dorfmüller P, Mercier O, Bogaard HJ, Postmus PE, Westerhof N, Stienen GJM, van der Laarse WJ, Vonk-Noordegraaf A, Ottenheijm CA. Diaphragm Muscle Fiber Weakness in Pulmonary Hypertension. Am J Respir Crit Care Med 183:1411-1418, 2010.

Lamberts RR, Onderwater G, Hamdani N, Vreden MJA, Steenhuisen J, Eringa EC, Loer SA, Stienen GJM, Bouwman RA. Reactive Oxygen Species-Induced Stimulation of 5’AMP-Activated Protein Kinase Mediates Sevoflurane-Induced Cardioprotection. Circulation 120, S10-S15, 2009.

Narolska NA, Piroddi N, Belus A, Boontje NM, Scellini B, Deppermann S, Zaremba R,  Musters RJ, dos Remedios C, Jaquet K, Foster DB, Murphy AM, van Eyk JE, Tesi C, Poggesi C, van der Velden J, Stienen GJM. Impaired diastolic function after exchange of endogenous troponin I with C-terminal truncated troponin I in human cardiac muscle. Circ Res 99, 1012-1020, 2006.

Warner Simonides

Research focus

Thyroid-hormone regulated gene expression in cardiac and skeletal muscle.

Warner Simonides studied Biochemistry at the State University Leiden, The Netherlands and obtained his Ph.D. with honors in 1985 for studies which identified a mechanism of skeletal-muscle contractile dysfunction in thyroid disease. He continued this research line as researcher at the Department of Physiology of the Free University, Amsterdam, which included a period at the Thyroid Division of the Brigham and Women’s Hospital, Harvard Medical School (1991-1993), where he identified one of the molecular mechanisms of thyroid-hormone action in muscle. He was appointed assistant professor (1999) and associate professor (2006) at the Department of Physiology of the VU University Medical Center, Amsterdam and the research line now also included cardiac action of thyroid hormone. He is co-founder and chairman of the Dutch Thyroid Research Foundation.
Funded by The Dutch Heart Foundation, ZonMW and the VUmc, altered cardiac metabolism of thyroid hormone was identified as a contributing factor in the development of heart failure in rat and mouse models of pulmonary hypertension and myocardial infarction. The principal focus of current research is on determining the molecular mechanisms and clinical relevance of cardiac-specific metabolism of thyroid hormone in chronic heart failure.

Selection of recent publications

Janssen R, Zuidwijk MJ, Muller A, van Mil A, Dirkx E, Oudejans CBM, Paulus WJ, Simonides WS. MicroRNA 214 is a potential regulator of thyroid hormone levels in the mouse heart following myocardial infarction, by targeting the thyroid-hormone inactivating enzyme deiodinase type III.  Front Endocrinol. Vol 7, doi: 10.3389/fendo.2016.00022, 2016

Salvatore D, Simonides WS, Dentice M, Zavacki AM, Larsen PR.Thyroid hormones and skeletal muscle-new insights and potential implications. Nature Rev Endocrinol 10, 206-214, 2014.

Janssen R, Zuidwijk MJ, Muller A, Mulders J, Oudejans CBM, Simonides WS. Cardiac expression of deiodinase type 3 (Dio3) following myocardial infarction is associated with the induction of a pluripotency microRNA signature from the Dlk1-Dio3 genomic region. Endocrinology 154, 1973-1978, 2013.

Pol CJ,  Muller A, Zuidwijk MJ, van Deel ED, Kaptein E, Saba A,  Marchini M, Zucchi R, Visser TJ, Paulus WJ, Duncker DJ, Simonides WS. Left-ventricular remodeling following myocardial infarction is associated with a cardiomyocyte-specific hypothyroid condition. Endocrinology 152, 669-679, 2011.

Redout EM, van der Toorn A, Zuidwijk MJ, van Beek-Harmsen BJ, van de Kolk CWA,
van Echteld CJA, Musters RJP, van Hardeveld C, Paulus WJ, Simonides WS. Antioxidant treatment attenuates pulmonary arterial hypertension-induced heart failure. Am J Physiol Heart Circ Physiol 298, H1038-H1047, 2010.

Simonides WS, Mulcahey MA, Redout EM, Muller A, Zuidwijk MJ, Visser TJ, Wassen FWJS, Crescenzi A, da-Silva WS, Harney J, Engel FB, Obregon MJ, Larsen PR, Bianco AC, Huang SA. Hypoxia-inducible factor induces local thyroid hormone inactivation in hypoxic-ischemic disease in rats. J Clin Invest  118: 975-983, 2008.

Ongoing research projects

Cardiac-specific activation of type III deiodinase following myocardial infarction: a therapeutic target?

The role of differential expression of deiodinases in skeletal muscle development and disease.

Coen Ottenheijm

Research focus

The regulatory and pathogenic role of myofilament proteins in striated muscle contraction.

Coen Ottenheijm received his doctorate at the dept of Pulmonology at the Radboud University Nijmegen Medical Center in 2006, where he investigated the contribution of myofilament dysfunction to diaphragm weakness in patients with Chronic Obstructive Pulmonary Disease. His PhD research prompted Dr. Ottenheijm to pursue a postdoctoral position in the lab of Dr. Henk Granzier at the University of Arizona (funded by a NWO Rubicon grant), where he focussed on the role of the giant myofilament proteins titin (the largest protein known to date) and nebulin in muscle function in health and disease. Subsequently, he moved to the Department of Physiology at VUmc to further increase his understanding of the role of nebulin and other myofilament proteins in muscle disease; this work was funded by a NWO VENI grant. Currently, Dr Ottenheijm is working at the Department of Physiology at VUmc – supported by a NWO VIDI grant – and is prinicipal investigator in two collaborative EU (FP7) funded studies investigating novel transgenic mouse models of nebulin-based nemaline myopathy. Furthermore, in collaboration with the departments of Intensive Care Medicine, Surgery and Anesthesiology at VUmc, Dr Ottenheijm’s research group focusses on the pathogenesis of diaphragm weakness in conditions associated with altered diaphragm activity, such as pulmonary hypertension and mechanical ventilation. In 2014, he received a R01 grant (National Institutes of Health) to support his diaphragm research.

Selection of recent publications

P. Hooijman, A. Beishuizen, MA Paul,…., and Ottenheijm CAC. Diaphragm fiber strength is reduced in critically ill patients and restored by a troponin activator. Am J Respir Crit Care Med. 2014. 189(7):863-5.

Ottenheijm CAC, Buck D, de Winter JM, Ferrara C. Piroddi N, Tesi C., Jasper JR, Malik FI, Meng H, Stienen GJM, Beggs AH, Labeit S, Poggesi C, Lawlor MW, Granzier H. Deleting exon 55 from the nebulin gene induces severe muscle weakness in a mouse model for nemaline myopathy. Brain. 2013. 136(Pt 6):1718-31.

de Winter JM, Buck D, Hidalgo C, Jasper JR, Malik FI, Clarke NF, Stienen GJM, Lawlor MW, Beggs AH,  Henk Granzier, Ottenheijm CAC. Troponin activator augments muscle force in nemaline myopathy patients with nebulin mutations. J. Med. Genet. 2013. 50(6):383-92.

Lassche S, Stienen GJ, Irving TC, van der Maarel SM, Voermans NC, Padberg GW, Granzier H, van Engelen BG, Ottenheijm CAC. Sarcomeric dysfunction contributes to muscle weakness in facioscapulohumeral muscular dystrophy. Neurology. 2013 Feb 19;80(8):733-7.

Manders E, de Man FS, Handoko ML, Westerhof N, van Hees HW, Stienen GJ, Vonk Noordegraaf A, Ottenheijm CAC. Diaphragm weakness in pulmonary arterial hypertension: role of sarcomeric dysfunction. Am J Physiol Lung Cell Mol Physiol. 2012 Dec 15;303(12):L1070-8.

Ongoing research projects

2014-2019 NIH; National Heart, Lung and Blood Institute; R01HL121500.
Title: Role of titin in the pathophysiology of diaphragm weakness during mechanical ventilation.

2012-2017 VIDI grant (career development); NWO
Title: Muscle weakness in nemaline myopathy: what is the cause and can it be treated?

2012-2017 EU, Marie Curie International Training Network grant.
Title: Sarcomere-based signalling in muscle remodelling (acronym: SarcoSi)

Alice Muller

RESEARCH INTEREST

The main research focus is the role of thyroid hormone metabolism in heart failure. Multiple signal-transduction pathways have been shown to be involved in the process of pathological hypertrophy and heart failure, and one of the factors that may play a role is reduced thyroid-hormone (TH) signaling. A condition of low TH-levels is characterized by a cardiac gene expression pattern that resembles that of the pathologically remodeling heart. Our group reported an almost complete impairment of cardiomyocyte-specific TH signaling in hypertension-induced RV failure in the rat as well as in chronic LV failure following myocardial infarction in mice. In both models this is associated with the re-induction in cardiomyocytes of the TH-degrading enzyme deiodinase type 3 (Dio3) and, as a result, reduced TH activity. Our current research is aimed at establishing the mechanism of Dio3 induction and the role of reduced cardiac TH signaling in pathological gene expression and cardiac dysfunction in chronic heart failure.

KEY PUBLICATIONS

MicroRNA 214 Is a Potential Regulator of Thyroid Hormone Levels in the Mouse Heart Following Myocardial Infarction, by Targeting the Thyroid-Hormone-Inactivating Enzyme Deiodinase Type III. Janssen R, Zuidwijk MJ, Muller A, van Mil A, Dirkx E, Oudejans CB, Paulus WJ,Simonides WS. Front Endocrinol. 2016; 7:22.

Janssen R, Zuidwijk MJ, Kuster DW, Muller A, Simonides WS. Thyroid Hormone-Regulated Cardiac microRNAs are Predicted to Suppress Pathological Hypertrophic Signaling. Front Endocrinol. 2014; 5:171.

Janssen R, Zuidwijk M, Muller A, Mulders J, Oudejans CB, Simonides WS. Cardiac expression of deiodinase type 3 (Dio3) following myocardial infarction is associated with the induction of a pluripotency microRNA signature from the Dlk1-Dio3 genomic region. Endocrinology. 2013; 154:1973-1978.

Pol CJ, Muller A, Zuidwijk MJ, van Deel ED, Kaptein E, Saba A, Marchini M, Zucchi R, Visser TJ, Paulus WJ, Duncker DJ, Simonides WS.Left-ventricular remodeling after myocardial infarction is associated with a cardiomyocyte-specific hypothyroid condition. Endocrinology. 2011; 152:669-679.

Simonides WS, Mulcahey MA, Redout EM, Muller A, Zuidwijk MJ, Visser TJ, Wassen FW, Crescenzi A, da-Silva WS, Harney J, Engel FB, Obregon MJ, Larsen PR, Bianco AC, Huang SA. Hypoxia-inducible factor induces local thyroid hormone inactivation during hypoxic-ischemic desease in rats. J Clin Invest. 2008; 118:975-983.

ONGOING RESEACH PROJECTS

Cardiac-specific activation of type III deiodinase following myocardial infarction: a therapeutic target?

The role of differential expression of deiodinases in skeletal muscle development and disease.

Peter Hordijk

RESEARCH INTERESTS

The integrity of the vascular wall is dependent on proper cell-cell contact between endothelial cells. This cell-cell contact is mediated by VE (Vascular Endothelial)-cadherin (CD144), a calcium-dependent homotypic adhesion molecule. The adhesive function of VE-cadherin is regulated in a dynamic fashion by both extracellular stimuli (VEGF, TNF, thrombin, as well as vessel wall stiffness, etc) and intracellular signalling. For the regulation of VE-cadherin, its link to the actin cytoskeleton, via its intracellular domain, is essential.

To increase our molecular insights in these events, our group focuses on the regulation of actin dynamics in the context of endothelial integrity. We are particularly interested in the role and regulation of Rho-like GTPases. We use a range of in vitro approaches including biochemical assays, high resolution imaging and electrical resistance measurements of endothelial monolayers. Recently, we identified several ubiquitin ligases that specifically regulate Rho proteins and, in this way, control endothelial integrity.
Related research activities aim to link our molecular studies in endothelial cells to human disease. In collaboration with our colleagues from the clinic, we focus specifically on hypertensive disorders and cardiac disease related to diastolic dysfunction.

KEY PUBLICATIONS 

1. Kovačević I, Sakaue T, Majoleé J, Pronk MC, Maekawa M, Geerts D, Fernandez-Borja M, Higashiyama S, Hordijk PL. The Cullin-3-Rbx1-KCTD10 complex controls endothelial barrier function via K63 ubiquitination of RhoB. J Cell Biol. 2018 Mar 5;217(3):1015-1032.
2. Reinhard NR, Mastop M, Yin T, Wu Y, Bosma EK, Gadella TWJ Jr, Goedhart J, Hordijk PL. The balance between Gα(i)-Cdc42/Rac and Gα(1)(2)/(1)(3)-RhoA pathways determines endothelial barrier regulation by sphingosine-1-phosphate. Mol Biol Cell. 2017 Nov 7;28(23):3371-3382.
3. Dorland YL, Malinova TS, van Stalborch AM, Grieve AG, van Geemen D, Jansen NS, de Kreuk BJ, Nawaz K, Kole J, Geerts D, Musters RJ, de Rooij J, Hordijk PL, Huveneers S. The F-BAR protein pacsin2 inhibits asymmetric VE-cadherin internalization from tensile adherens junctions. Nat Commun. 2016 Jul 15;7:12210.
4. Reinhard NR, van Helden SF, Anthony EC, Yin T, Wu YI, Goedhart J, Gadella TW, Hordijk PL. Spatiotemporal analysis of RhoA/B/C activation in primary human endothelial cells. Sci Rep. 2016 6:25502.
5. Huveneers S, Daemen MJ, Hordijk PL. Between Rho(k) and a hard place: the relation between vessel wall stiffness, endothelial contractility, and cardiovascular disease. Circ Res. 2015 ;116(5):895-908.

Diederik Kuster

Research interests

My research has focused on understanding molecular changes that underlie cardiac muscle function, hypertrophy and 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). Combining biochemistry, mass-spectrometry and muscle mechanics, I identified a novel phosphorylation site on cMyBP-C, which was phosphorylated by GSK3β, and which increased the kinetics of contraction. Additionally, I identified an HCM-specific miRNA signature in HCM-patients with cMyBP-C mutations.

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 MYBPC3Δ25bp mutation. In 2013, I received the post-doctoral fellowship from the American Heart Association to work on the MYBPC3Δ25bp mutation.

My current research at the VUmc focuses on molecular changes in HCM mouse models and human patient samples. 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

1. Najafi A, Sequeira V, Helmes M, Bollen IA, Goebel M, Regan JA, Carrier L, Kuster DW, Van Der Velden J. Selective phosphorylation of PKA targets after β-adrenergic receptor stimulation impairs myofilament function in Mybpc3-targeted HCM mouse model. Cardiovasc Res. 2016 110:200-214

2. Sequeira V, Najafi A, Wijnker PJ, Dos Remedios CG, Michels M, Kuster DW, van der Velden J. ADP-stimulated contraction: A predictor of thin-filament activation in cardiac disease. Proc Natl Acad Sci U S A. 2015 ;112(50):E7003-12.

3. 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

4. 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

5. Kuster DW, Mulders J, ten Cate FJ, Michels M, dos Remedios CG, da Costa Martins PA, van der Velden J, Oudejans CB. MicroRNA transcriptome profiling in cardiac tissue of hypertrophic cardiomyopathy patients with MYBPC3 mutations. J Mol Cell Cardiol 2013 65:59-66

 


Selection of funded projects:

I can see clearly now: small animal imaging to distinguish cause and effect in early HCM disease pathology. ACS out-of-the-box grant 2016-2018

Pathophysiology of Hypertrophic Cardiomyopathy Associated Cardiac Myosin Binding Protein-C Mutation. American Heart Association Post-doctoral fellowship grant (2013-2015)

 


Group members

PhD students (co-promotor)
Aref Najafi
Louise Nijenkamp
Ilse Bollen
Maike Schuldt
Larissa Dorsch

Technician
Max Goebel

 

Pieter Koolwijk

Research focus

Vascular aspects of Tissue Engineering

Pieter Koolwijk studied Medical Biology at the University of Amsterdam and received a PhD degree from the University of Utrecht in 1990 for his studies on the characteristics of bispecific monoclonal antibodies. From November 1989 till March 2006 he was projectleader/senior investigator at Gaubius Laboratory TNO-QoL in Leiden, where he studied the involvement of proteolytic enzymes, matrix components and hypoxia on the process of angiogenesis. During this period his group developed many in vitro and in vivo angiogenesis models, and he was, as projectleader, responsible for the coordination of contract research in the field of angiogenesis for pharmaceutical companies.  In April 2006, he and a part of his group moved to the Institute for Cardiovascular Research VU (ICaR-VU), Dept. for Physiology, VUMC in Amsterdam, and continued his work on the involvement of hypoxia and temporary fibrin matrices on angiogenesis. In collaboration with Victor van Hinsbergh’s group, his group has made important contributions on the effect of chronic hypoxia on endothelial cell functions and endothelial cell progenitor differentiation/outgrowth in relation to vascularization of tissue-engineered tissue constructs.

Selection of recent publications

Nauta TD, van Hinsbergh VW, Koolwijk P (2014). Hypoxic signaling during tissue repair and regenerative medicine. Int. J. Mol. Sci. 15, 19791-815.

Weijers E.M., van den Broek L.J., Waaijman T., van Hinsbergh V.W.M., Gibbs S., Koolwijk P. The influence of hypoxia and fibrinogen variants on the expansion and differentiation of adipose tissue-derived mesenchymal stem cells. Tissue Engineering A. 2011, 17:2675-85.

Rensing, K.L., von der Thüsen, J.J., Weijers, E.m., Houttuijn-Bloemendaal, F.M., van Lammeren, G.W., Vink, A., van de Wal, A.C., van Hinsbergh, V.W.M., van der Loos, G.M., Stroes, E.S., Koolwijk, P., Twickler, M. Endothelial insulin receptor expression in human atherosclerotic plaques: linking micro- and macrovascular disease in diabetes? Atherosclerosis 2012, 222:208-15

Weijers EM, Van Wijhe MH, Joosten L, Horrevoets AJ, de Maat MP, van Hinsbergh VW, Koolwijk P. Molecular weight fibrinogen variants alter gene expression and functional characteristics of human endothelial cells. J Thromb Haemost. 2010, 8:2800-9.

van Beem, R.T., Verloop, R.E., Kleijer, M., Noort, W.A., Loof, N., Koolwijk, P., van der Schoot, C.E.,  van Hinsbergh, V.W.M. Zwaginga, J.J. Blood outgrowth endothelial cells from cord blood and peripheral blood: Angiogenesis-related characteristics in vitro. J Thromb Haemost. 2009, 7:217-226.

Ongoing research projects

2011-2015 NIRM project (Netherlands Institute Regenerative Medicine)
Angiogenesis: generating new vessels (project leader WP 1.6, 6 fte)