• Male

Dr. S. Huveneers

Position: Scientific staff member (UD)
Main activities: Research
Specialisation: Vascular Microenvironment & Integrity
foto
Focus of research:

www.huveneerslab.eu

Endothelial mechanotransduction in inflammation and vascular disease
Within blood vessels, endothelial cell-cell and cell-matrix adhesions are crucial to preserve barrier function, and these adhesions are tightly controlled during vascular development, angiogenesis and transendothelial migration of inflammatory and tumor cells. Endothelial cells respond to mechanical changes in the vasculature by a complex array of intracellular biochemical and structural changes. This mechanotransduction response include signals that promote, but also signals that protect against, monolayer permeability. Excessive extracellular matrix (ECM) stiffening during aging disturbs this balance and causes permeability and inflammation in vascular disease and acute respiratory distress syndrome. In addition, increased stiffness is an early sign of vascular damage after chemo- or radiotherapy. Surprisingly, the underlying molecular events that control stiffness-induced mechanotransduction remain elusive. To achieve this we study the endothelium in the physiological setting of the vascular wall and recently discovered that differences in wall stiffness of human arterial and venous vessels modulate endothelial adhesions . 

Molecular changes at the VE-cadherin complex that regulate endothelial integrity
The integrity of endothelial cell-cell adhesions is  regulated in space and time during angiogenesis and inflammation. To achieve this, VE-cadherin, the central component of endothelial cell-cell adhesions, is targeted by many major vascular signaling pathways. However, the molecular effects of angiogenic or inflammatory signals on the VE-cadherin complex, that may explain the tight spatiotemporal control of cell-cell adhesion, remain largely unclear. It is known that local organization of the actin cytoskeleton plays an important role in regulating the VE-cadherin complex. Identifying the molecular changes at the VE-cadherin-based adhesion that occur upon cytoskeletal-dependent remodeling, and unveiling their dynamics at cell-cell junctions in response to signals will be key to understand the control of endothelial cell-cell adhesion during angiogenesis and inflammation. Our previous publications and current preliminary data show that the molecular composition of endothelial cell-cell adhesions in response to permeability signals (VEGF and thrombin), is different from that of mature/linear adhesions. Vinculin and other proteins specifically associate with the active subset of VE-cadherin-adhesions (Focal Adherens Junctions) that is linked to, and dependent on, the contractile actin cytoskeleton. We are elucidating the molecular regulation of the VE-cadherin complex.

AMC themes: Cardiovascular Diseases, Infection & Immunity
Departments: Medical Biochemistry
Dorland YL, Huveneers S, Cell-cell junctional mechanotransduction in endothelial remodeling. CELL MOL LIFE SCI 2017;74 (2):279-292 [PubMed]
Dorland YL, Malinova TS, van Stalborch AMD, Grieve AG, van Geemen D, Jansen NS, de Kreuk BJ, Nawaz K, Kole J, Geerts D, Musters RJP, de Rooij J, Hordijk PL, Huveneers S, The F-BAR protein pacsin2 inhibits asymmetric VE-cadherin internalization from tensile adherens junctions. NAT COMMUN 2016;7:12210 [PubMed]
Heemskerk N, Schimmel L, Oort C, van Rijssel J, Yin T, Ma B, van Unen J, Pitter B, Huveneers S, Goedhart J, Wu Y, Montanez E, Woodfin A, van Buul JD, F-actin-rich contractile endothelial pores prevent vascular leakage during leukocyte diapedesis through local RhoA signalling. NAT COMMUN 2016;7:10493 [PubMed]
Fraccaroli A, Pitter B, Taha AA, Seebach J, Huveneers S, Kirsch J, Casaroli-Marano RP, Zahler S, Pohl U, Gerhardt H, Schnittler HJ, Montanez E, Endothelial Alpha-Parvin Controls Integrity of Developing Vasculature and Is Required for Maintenance of Cell-Cell Junctions. CIRC RES 2015;117 (1):29-40 [PubMed]
Hamers AAJ, van Dam L, Teixeira Duarte JM, Vos M, Marinković G, van Tiel CM, Meijer SL, van Stalborch AM, Huveneers S, te Velde AA, de Jonge WJ, de Vries CJM, Deficiency of Nuclear Receptor Nur77 Aggravates Mouse Experimental Colitis by Increased NFκB Activity in Macrophages. PLOS ONE 2015;10 (8):e0133598 [PubMed]
Huveneers S, Daemen MJAP, 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 [PubMed]
Oldenburg J, van der Krogt G, Twiss F, Bongaarts A, Habani Y, Slotman JA, Houtsmuller A, Huveneers S, de Rooij J, VASP, zyxin and TES are tension-dependent members of Focal Adherens Junctions independent of the alpha-catenin-vinculin module. SCI REP-UK 2015;5:17225 [PubMed]
Timmerman I, Heemskerk N, Kroon J, Schaefer A, van Rijssel J, Hoogenboezem M, van Unen J, Goedhart J, Gadella TWJ Jr, Yin T, Wu Y, Huveneers S, van Buul JD, A local VE-cadherin and Trio-based signaling complex stabilizes endothelial junctions through Rac1. J CELL SCI 2015;128 (16):3041-3054 [PubMed]
Timmerman I, Heemskerk N, Kroon J, Schaefer A, van Rijssel J, Hoogenboezem M, van Unen J, Goedhart J, Gadella TWJ Jr, Yin T, Wu Y, Huveneers S, van Buul JD, A local VE-cadherin and Trio-based signaling complex stabilizes endothelial junctions through Rac1 (vol 128, pg 3041, 2015). J CELL SCI 2015;128 (18):3514 [PubMed]
Hamers AAJ, Uleman S, van Tiel CM, Kruijswijk D, van Stalborch AM, Huveneers S, de Vries CJM, van 't Veer C, Limited role of nuclear receptor Nur77 in Escherichia coli-induced peritonitis. INFECT IMMUN 2014;82 (1):253-264 [PubMed]
van Buul JD, Geerts D, Huveneers S, Rho GAPs and GEFs Controling switches in endothelial cell adhesion. CELL ADHES MIGR 2014;8 (2):108-124 [PubMed]
van Geemen D, Smeets MWJ, van Stalborch AMD, Woerdeman LAE, Daemen MJAP, Hordijk PL, Huveneers S, F-actin-anchored focal adhesions distinguish endothelial phenotypes of human arteries and veins. ARTERIOSCL THROM VAS 2014;34 (9):2059-2067 [PubMed]
Huveneers S, de Rooij J, Mechanosensitive systems at the cadherin-F-actin interface. J CELL SCI 2013;126 (2):403-413 [PubMed]
Aman J, van Bezu J, Damanafshan A, Huveneers S, Eringa EC, Vogel SM, Groeneveld ABJ, Vonk Noordegraaf A, van Hinsbergh VWM, van Nieuw Amerongen GP, Effective treatment of edema and endothelial barrier dysfunction with imatinib. CIRCULATION 2012;126 (23):2728-2738 [PubMed]
Huveneers S, Oldenburg J, Spanjaard E, van der Krogt G, Grigoriev I, Akhmanova A, Rehmann H, de Rooij J, Vinculin associates with endothelial VE-cadherin junctions to control force-dependent remodeling. J CELL BIOL 2012;196 (5):641-652 [PubMed]
Twiss F, Le Duc Q, van der Horst S, Tabdili H, van der Krogt G, Wang N, Rehmann H, Huveneers S, Leckband DE, de Rooij J, Vinculin-dependent Cadherin mechanosensing regulates efficient epithelial barrier formation. BIOL OPEN 2012;1 (11):1128-U120 [PubMed]
Pannekoek WJ, van Dijk JJG, Chan OYA, Huveneers S, Linnemann JR, Spanjaard E, Brouwer PM, van der Meer AJ, Zwartkruis FJT, Rehmann H, de Rooij J, Bos JL, Epac1 and PDZ-GEF cooperate in Rap1 mediated endothelial junction control. CELL SIGNAL 2011;23 (12):2056-2064 [PubMed]
Huveneers S, Danen EHJ, The Interaction of Src Kinase with beta 3 Integrin Tails: A Potential Therapeutic Target in Thrombosis and Cancer. SCI WORLD J 2010;10:1100-1105 [PubMed]
Huveneers S, Danen EHJ, Adhesion signaling - crosstalk between integrins, Src and Rho. J CELL SCI 2009;122 (8):1059-1069 [PubMed]
Puigvert JC, Huveneers S, Fredriksson L, op het Veld M, van de Water B, Danen EHJ, Cross-Talk between Integrins and Oncogenes Modulates Chemosensitivity. MOL PHARMACOL 2009;75 (4):947-955 [PubMed]
Huveneers S. The regulation of Rho and Src signaling by integrins. s.l.: s.n.; 2008. 128p. ISBN 9789090234434 [UvA Dissertations Online] Proefschrift Universiteit van Amsterdam. (Promotor(s): Berns AJM; copromotor(s): Danen EHJ)
Huveneers S, Arslan S, van de Water B, Sonnenberg A, Danen EHJ, Integrins uncouple src-induced morphological and oncogenic transformation. J BIOL CHEM 2008;283 (19):13243-13251 [PubMed]
Huveneers S, Truong H, Fässler R, Sonnenberg A, Danen EHJ, Binding of soluble fibronectin to integrin alpha 5 beta 1 - link to focal adhesion redistribution and contractile shape. J CELL SCI 2008;121 (15):2452-2462 [PubMed]
Huveneers S, Truong H, Danen HJ, Integrins: Signaling, disease, and therapy. INT J RADIAT BIOL 2007;83 (11-12):743-751 [PubMed]
Huveneers S, van den Bout I, Sonneveld P, Sancho A, Sonnenberg A, Danen EHJ, Integrin alpha(v)beta(3) controls activity and oncogenic potential of primed c-Src. CANCER RES 2007;67 (6):2693-2700 [PubMed]
van den Bout I, Truong HH, Huveneers S, Kuikman I, Danen EHJ, Sonnenberg A, The regulation of MacMARCKS expression by integrin beta 3. EXP CELL RES 2007;313 (6):1260-1269 [PubMed]
Danen EHJ, van Rheenen J, Franken W, Huveneers S, Sonneveld P, Jalink K, Sonnenberg A, Integrins control motile strategy through a Rho-cofilin pathway. J CELL BIOL 2005;169 (3):515-526 [PubMed]
Malliri A, van Es S, Huveneers S, Collard JG, The Rac exchange factor Tiam1 is required for the establishment and maintenance of cadherin-based adhesions. J BIOL CHEM 2004;279 (29):30092-30098 [PubMed]
van Oort E, de Heer PG, van Leeuwen WA, Derksen NIL, Müller M, Huveneers S, Aalberse RC, van Ree R, Maturation of Pichia pastoris-derived recombinant pro-Der p 1 induced by deglycosylation and by the natural cysteine protease Der p 1 from house dust mite. EUR J BIOCHEM 2002;269 (2):671-679 [PubMed]
Key publications

Dorland YL, Huveneers S, Cell-cell junctional mechanotransduction in endothelial remodeling. CELL MOL LIFE SCI 2017;74 (2):279-292 [PubMed]
Dorland YL, Malinova TS, van Stalborch AMD, Grieve AG, van Geemen D, Jansen NS, de Kreuk BJ, Nawaz K, Kole J, Geerts D, Musters RJP, de Rooij J, Hordijk PL, Huveneers S, The F-BAR protein pacsin2 inhibits asymmetric VE-cadherin internalization from tensile adherens junctions. NAT COMMUN 2016;7:12210 [PubMed]
Huveneers S, Daemen MJAP, 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 [PubMed]
van Geemen D, Smeets MWJ, van Stalborch AMD, Woerdeman LAE, Daemen MJAP, Hordijk PL, Huveneers S, F-actin-anchored focal adhesions distinguish endothelial phenotypes of human arteries and veins. ARTERIOSCL THROM VAS 2014;34 (9):2059-2067 [PubMed]
Huveneers S, Oldenburg J, Spanjaard E, van der Krogt G, Grigoriev I, Akhmanova A, Rehmann H, de Rooij J, Vinculin associates with endothelial VE-cadherin junctions to control force-dependent remodeling. J CELL BIOL 2012;196 (5):641-652 [PubMed]


All Publications

Curriculum Vitae

2016-now Groupleader at the Academic Medical Center, University of Amsterdam 

2016-now Vice-chair of the association of researchers in the talent scheme of NWO (VVViO

2015 NWO-VIDI fellowship

2012-2016 Group leader at Sanquin Research (Amsterdam)

2010 NWO-VENI fellowship

2010-now Board member of the Dutch Endothelial Biology Society 

2008-2012 Postdoc at the Hubrecht Institute (Utrecht)

2003-2008 PhD student at the Netherlands Cancer Institute (Amsterdam) & at Leiden University (Leiden)

 

Research programmes

Prof. dr. C.J.M. de Vries (Regulation of Vascular Homeostasis and Metabolism)

Prof. dr. P.L. Hordijk (Landsteiner Laboratory)

Other research related activities
  • None reported
Current research funding
  • AMC (Vrijgesteld)
  • NWO