My research in the field of vascular cell biology aims to characterize the molecular, structural, and functional abnormalities of pulmonary vascular endothelial cells (pEC) in lung diseases. The verdict is that phenotypically altered cells cannot adapt to micro-environmental changes. These miss-adaptations lead to sustained cell activation and drive disease-characteristic lung vascular changes. With my background in biomedical engineering, I aim to replicate human diseases in the laboratory by using complex culture systems and functional experimentation. For example, my PhD project investigated the impact of biomechanical forces, such as increased blood flow velocity, as triggers of activation and injury in pulmonary hypertension (PH). In my post-doc modern transcriptomic and proteomic approaches are employed to dissect and correct underlying signaling and further characterize the functional unit of endothelium and its micro-environment in lung health and disease.
Central for my work is the continuous extension of our biobank that comprises several types of human endothelial cells, smooth muscle cells, and fibroblasts. Currently we are expanding our research focus on the role of the vascular endothelium in lung diseases such as chronic thromboembolic pulmonary hypertension (CTEPH), pulmonary veno-occlusive disease (PVOD), and chronic obstructive pulmonary disease (COPD).
I am a biomedical engineer by training and did a PhD in vascular cell biology and physiology at the VU University Medical Center (VUmc) in Amsterdam. During that time, my work became more translational and focused on the deadly lung disorder of PH through my affiliation with the clinical dept. of Pulmonary Diseases. I went to Harvard Medical School to get acquainted with the role of loss- and gain-of-function mutations in the bone morphogenetic protein receptor type II (BMPRII) in preparation of my first postdoctoral position. These mutations are of central importance in different pathologies including PH. My postdoctoral research is supervised by Prof. Goumans and set within a large-scale Dutch national program with the aim to identify compounds to restore the TGFβ/BMP balance in PH and associated right heart failure.
Delayed microvascular shear adaptation in pulmonary arterial hypertension. Role of platelet endothelial cell adhesion molecule-1 cleavage.
Szulcek R, Happe CM, Rol N, Fontijn RD, Dickhoff C, Hartemink KJ, Grunberg K, Tu L, Timens W, Nossent GD, Paul MA, Leyen TA, Horrevoets AJ, de Man FS, Guignabert C, Yu PB, Vonk-Noordegraaf A, van Nieuw Amerongen, GP, Bogaard HJ.
Am J Respir Crit Care Med 2016; 193: 1410–1420.
Transient intervals of hyper-gravity enhance endothelial barrier integrity: Impact of mechanical and gravitational forces measured electrically
Szulcek R, van Bezu J, Boonstra J, van Loon JJWA, van Nieuw Amerongen GP.
PLoS ONE 2015; 10: e0144269
Localized RhoA GTPase activity regulates dynamics of endothelial monolayer integrity.
Szulcek R, Beckers CML, Hodzic J, de Wit J, Chen Z, Grob T, Musters RJP, Minshall RD, van Hinsbergh VW, van Nieuw Amerongen GP.
Cardiovasc Res 2013; 99: 471–482.
Groups: Cardiovascular Cell Biology