Research & Educational staff: Dr. Margot Bartelings, Dr. Beerend Hierck, Dr. Egbert Lakke, Dr. Monique Jongbloed, Dr. Robert Notenboom, Dr. Paul Gobée, Drs. Friso Jansen, Drs. Daniel Jansma, Bas Blankevoort
Skills lab: Job Aarents, Judith den Boeft, Fred van Immerseel
PhDs: Yang Ge, Claire Glashan, Joshua Peterson, Vera van de Pol
Technicians: ing. Conny van Munsteren, ing. Bert Wisse
The central focus of the research group is the development and pathomorphology of the heart, with emphasis on the cardiovascular outflow tract of the heart. We focus on the role of the extracardiac contributions of the neural crest, epicardium and second heart field and how disturbed signalling will result in outflow tract malformations. We uses both animal models as wells as human tissues.
The group works closely together with the research group of Dr Monique Jongbloed .
Aim and focus
To provide better mechanistic insights in the pathomorphology of patients our human studies are paralleled by studies in well-defined mouse and chicken models to unravel the role of extracardiac contributors (second heart field, neural crest and epicardium) in the differentiation and maturation of the aortic root. The analyses include a range of immunohistochemistry and molecular biological approaches (ao single cell sequencing, micro array analysis), in combination with (genetic cre-lox system and non-genetic fluorescent dye microinjections) cell lineage tracing techniques, genetic models for bicuspid aortic valves (e.g.Nos3 and Hoxa1 knock out mouse models), laser dissection microscopy, in vitro flow experiments, electrophysiology, optical mapping and ultrasound evaluations of embryonic cardiac function. With these techniques we explore the hypothesis that processes essential for normal embryonic cardiovascular patterning and differentiation are also involved in the maintenance and repair of the heart and vessel wall (Figure 1). Small deviations in the signaling processes can result into congenital cardiovascular malformations seen perinatal, but also into increased susceptibility of cardiovascular pathology seen in adults.
Figure 1 - The parietal cushion (P) gives rise to the right (RC)- and non-coronary (NC) aortic leaflets. The left coronary (LC) leaflet originates from the septal cushion (S). NKX2.5 positive second heart field cells are green. The endothelial cells are PECAM-1 positive (red). Asterix indicates region of endothelial infolding resulting in a NC and RC leaflet. Second heart field cells are present in the RC and NC, but not in the LC. Scale bars: 50µm.
Next to the cardiovascular research the Section of Clinical and Surgical Anatomy has a consultant function in surgical research. We support, supervise and/or coordinate research in close collaboration with clinical departments on new relevant neuroanatomical, orthopedic, abdominal and pelvic surgical scientific questions and surgical procedures. A major part of these studies concerns the development of nerve preservation techniques to reduce postoperative morbidity after complex surgery. A long-term objective to overcome these surgical problems we develop a unique 3D surgical planning system based on high resolution digitized histological sections of the human.Collaboration within the LUMC
Shared projects with the departments of Cell and Chemical Biology (Prof MJ Goumans), Cardiology (ao Dr MRM Jongbloed; Dr HM Siebeling; Prof M Schalij; Prof K Zeppenfeld), Thoracic surgery (Dr N Grewal and Prof R Klautz)
Active collaborations with shared projects: ErasmusMC (Prof J. Roos), University of Antwerp (Prof B Loeys), University of Leuven (Prof A Zwijssen), Universitas Indonesia (Prof I Kurnia Liem), University of Groningen (Dr T Plösch); University Medical Center Hamburg (Dr E Girdauskas).
Grants and other funding
NHS-2013T093; JW Roos-Hesselink en B Loeys. Unravelling aetiology and risk factors in patients with a bicuspid aortic valve. Consortium between ErasmusMC, RadboudMC en LUMC. Project ends in 2019.
2016: EU H2020-FTIPilot-2015-1; SURGassist 700925; A novel 3D Stereoscopic e-learning Solution for theoretical Surgical Training. Project ends in 2019.
van de Pol V, Kurakula K, DeRuiter MC, Goumans MJ. Thoracic Aortic Aneurysm Development in Patients with Bicuspid Aortic Valve: What Is the Role of Endothelial Cells? Front Physiol. 2017 Nov 30;8:938.
Vicente-Steijn R, Kelder TP, Tertoolen LG, Wisse LJ, Pijnappels DA, Poelmann RE, Schalij MJ, DeRuiter MC, Gittenberger-de Groot AC, Jongbloed MRM. RHOA-ROCK signalling is necessary for lateralization and differentiation of the developing sinoatrial node. Cardiovasc Res. 2017 Aug 1;113(10):1186-1197.
Baardman ME, Zwier MV, Wisse LJ, Gittenberger-de Groot AC, Kerstjens-Frederikse WS, Hofstra RM, Jurdzinski A, Hierck BP, Jongbloed MR, Berger RM, Plösch T, DeRuiter MC. Common arterial trunk and ventricular non-compaction in Lrp2 knockout mice indicate a crucial role of LRP2 in cardiac development. Dis Model Mech. 2016 Apr;9(4):413-25.
Bökenkamp R, van Brempt R, van Munsteren JC, van den Wijngaert I, de Hoogt R, Finos L, Goeman J, Groot AC, Poelmann RE, Blom NA, DeRuiter MC. Dlx1 and Rgs5 in the ductus arteriosus: vessel-specific genes identified by transcriptional profiling of laser-capture microdissected endothelial and smooth muscle cells. PLoS One. 2014 Jan 28;9(1).
Grewal N, Gittenberger-de Groot AC, Poelmann RE, Klautz RJ, Lindeman JH, Goumans MJ, Palmen M, Mohamed SA, Sievers HH, Bogers AJ, DeRuiter MC. Ascending aorta dilation in association with bicuspid aortic valve: a maturation defect of the aortic wall. J Thorac Cardiovasc Surg. 2014 Oct;148(4):1583-90.
Alkemade FE, van Vliet P, Henneman P, van Dijk KW, Hierck BP, van Munsteren JC, Scheerman JA, Goeman JJ, Havekes LM, Gittenberger-de Groot AC, van den Elsen PJ, DeRuiter MC. Prenatal exposure to apoE-deficiency and postnatal hypercholesterolemia are associated with altered cell-specific lysine methyltransferase and histone methylation patterns in the vasculature. Am J Pathol. 2010;176(2):542-8.
Clinical and Surgical Anatomy
Glashan CA, Androulakis AFA, Tao Q, Glashan RN, Wisse LJ, Ebert M, DeRuiter MC, van Meer BJ, Brouwer C, Dekkers OM, Pijnappels DA, de Bakker JMT, de Riva M, Piers MRD, Zeppenfeld K. Whole human heart histology to validate electroanatomical voltage mapping in patients with non-ischemic cardiomyopathy and ventricular tachycardia. European Heart Journal. 2018. In press.
Kraima AC, West NP, Treanor D, Magee DR, Bleys RL, Rutten HJ, van de Velde CJ, Quirke P, DeRuiter MC. Understanding the surgical pitfalls in total mesorectal excision: Investigating the histology of the perirectal fascia and the pelvic autonomic nerves. Eur J Surg Oncol. 2015.
Kleppe M, Kraima AC, Kruitwagen RF, Van Gorp T, Smit NN, van Munsteren JC, DeRuiter MC. Understanding Lymphatic Drainage Pathways of the Ovaries to Predict Sites for Sentinel Nodes in Ovarian Cancer. Int J Gynecol Cancer. 2015 Oct;25(8):1405-14.
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