Paul van Bergen en Henegouwen: Molecular Oncology

CVResearchProjectsLab membersPublications

 


paul Dr. Paul van Bergen en Henegouwen
Cell Biology
Faculty of Science, Utrecht University
Kruytgebouw, room N506
Padualaan 8, 3584 CH, Utrecht
The Netherlands
e-mail: p.vanbergen@uu.nl

 


Curriculum Vitae

Paul van Bergen en Henegouwen studied biology at the University of Amsterdam and received his PhD in 1986 at the Utrecht University. Postdoctoral training was performed at the Utrecht University in the group of prof. Dr. A.J. Verkleij, in Toulouse, France in the group of prof. dr. H. Chap, ISERM Unit 326, and at the Rockefeller University in New York in the group of prof. dr. H. Hanafusa. In 1995 he joined the Cell Biology group at the Utrecht University, where he is currently an associate professor.

 


Research summary

Control of growth factor signaling
Cell proliferation is stimulated by the action of growth factor receptors. Overexpression and mutations in these receptors are frequently involved in the development of cancer. In my research I focus on the negative feedback control of growth factor signaling. The model system I am interested in are the ErbB-receptors such as the receptor for the epidermal growth factor or EGFR. The most important negative feedback system for this receptor system is the receptor down regulation: upon activation, ErbB-Rs are internalized and transported to lysosomes where they are degraded. We study the regulatory mechanism of receptor internalization and trafficking in live cells using advanced light microscopical techniques.

Nanobodies
Important for studying the behavior of molecules in the live cells is the use of fluorescent markers such as fused fluorescent proteins or by labeling proteins using fluorescent antibodies. To reduce the effect of marker size we are using antibody fragments from the variable heavy chain of heavy-chain-only antibodies (VHH) from Llama glama, which are also called nanobodies. These are proteins of 15 kDa that can directly be conjugated to a fluorophore. Nanobodies or VHHs can be selected by phage display and can bind to any different protein or lipid.

antibody
Conventional antibody
Heavy and light chains
Both required for antigen binding
and stability
Heavy chain only antibody
Only heavy chains
Full antigen binding capacity
and stable

We have selected nanobodies against the EGFR, Her2 and Her3, and other tumor targets such as IGF-1R and Met. These nanobodies have affinities for their target proteins in the low nanoMolar ranges and because of their small size they have excellent penetration into tissues. We are using the nanobodies in our cell imaging studies, as novel anti-cancer therapeutics, and with in vivo imaging of tumor tissue.

 


Projects

1. What is the intitial step in receptor internalization?
Different post-translational modifications of the EGFR contribute to the internalization. Next to inducing kinase activity, EGF is also inducing the oligomerization or clustering of the EGFR. To study clustering we have set up the homo-FRET technology, which allows for a quantitative analysis of receptor clustering with subcellular resolution (Bader 2009, 2011). We have monitored the dimerization and oligomerization state of the EGFR. It appears that 40% of the EGFR is already dimerized in the resting cell (Hofman 2010). Receptor oligomerization occurs immediately after EGF binding and it is a kinase dependent process. We are currently investigating factors controlling EGFR oligomerization.

egfr_1

 

 

 

 

 

 

 

Homo-FRET imaging of EGFR clustering: color change indicates clustering after 10 min of EGF treatment, which is absent in cells expressing kinase dead EGFR (EGFR-K721A).

2. What factors are regulating vesicular transport of EGFR containing vesicles?
EGFRs are internalized via two different pathways: a clathrin-dependent and independent process. After internalization, coated- and non-coated vesicles are transported to the early endosome. To study the regulation of this transport step we are using Total Internal Reflection Fluorescence Microscopy or TIRF. We have found that the transport of EGFR containing intracellular vesicles is kinase dependent. In this project we focus on the signaling molecules that are regulating this process.

 

 

 

 

 

 

 

 

Internalization of EGF: EGF is labeled with Alexa488 and applied to EGFR expressing cells for 10 min. Cell are stained with anti-EEA1 for demarking early endosomes. Colocalization of EGF/EGFR complexes woth ealy endosomes is already seen which will further increase in time.

3. Nanobodies for tumor therapy
Selection by phage display allows for the generation of nanobodies that block ligand binding. We have selected a set of nanobodies against the EGFR that block binding of EGF (Roovers 2007). Epitope mapping shows that most of them are binding to domain III of the EGFR. Combination of two different anti-domain III nanobodies into one molecule (biparatopic nanobody)shows excellent blocking of ligand binding but poor effects on tumor growth (Roovers 2011). To optimize antitumor efficacy, we have made fusions of anti-EGFR nanobodies with sTRAIL, a ligand for the death receptor. Neural stem cells (NSC) were modified to express and secrete these fusion proteins. We have found that these variants of EGFR specific nanobodies released from NCSs specifically located to brain tumors induce a signficant reduction in tumor growth (Van de Water et al. 2012).

4. Nanobodies for in vivo imaging
Current technologies for targeted imaging of tumor tissue include immune-PET/SPECT and optical imaging. Antibodies are frequently used for the targetting of the different tracers to the tumor: radiotracers for PET and SPECT, and fluorescent dyes such as IRDye800CW for optical imaging. Optimal imaging, with high contrast, is obtained using probes that accumulate rapidly in the tumor while non-bound probes are rapidly cleared. The small size of the nanobody makes this an excellent probe for in vivo imaging; they accumulate within 2-4 hrs in the tumor while having in vivo half life of ~2 hrs.  We have used nanobodies against EGFR and Her2 to demonstrate their application in the imaging of xenografts in mice (Vosjan 2011; Oliveira 2012).

In vivo optical molecular imaging.  Athymic nude mice bearing A431 human tumor xenografts at both hind legs were intravenously injected with the anti-EGFR nanobody 7D12-IR, control nanobody R2-IR, or mouse monoclonal antibody against EGFR cetuximab-IR, and imaged under anesthesia at several time points post injection. A, Images of mice were taken with the optical imaging system at 30 min and 24 hours post injection (p.i.), in which tumors are indicated with red arrows and kidneys with green arrows.


Lab members

Postdocs:  
Dušan Popov-Čeleketić d.popov-celeketic@uu.nl
   
PhD students:  
Katerina Xenaki a.t.xenaki@uu.nl
Sara Pompe sara.pompe@gmx.de
Hui Wang H_Wang2016@hotmail.com
   
Technicians:  
Sofia Doulkeridou s.doulkeridou@uu.nl

 


 Publications

2016

de Bruin RC, Stam AG, Vangone A, van Bergen En Henegouwen PM, Verheul HM, Sebestyen Z, Kuball J, Bonvin AM, de Gruijl TD, and van der Vliet HJ. Prevention of Vgamma9Vdelta2 T Cell Activation by a Vgamma9Vdelta2 TCR Nanobody. J Immunol, 2017. 198(1): 308-317.

Kaplan M, Narasimhan S, de Heus C, Mance D, van Doorn S, Houben K, Popov-Celeketic D, Damman R, Katrukha EA, Jain P, Geerts WJ, Heck AJ, Folkers GE, Kapitein LC, Lemeer S, van Bergen En Henegouwen PM, and Baldus M. EGFR Dynamics Change during Activation in Native Membranes as Revealed by NMR. Cell, 2016. 167(5): 1241-1251 e11.

Salema V, Manas C, Cerdan L, Pinero-Lambea C, Marin E, Roovers RC, Van Bergen En Henegouwen PM, and Fernandez LA. High affinity nanobodies against human epidermal growth factor receptor selected on cells by E. coli display. MAbs, 2016. 8(7): 1286-1301.

Afsari HS, Cardoso Dos Santos M, Linden S, Chen T, Qiu X, van Bergen En Henegouwen PM, Jennings TL, Susumu K, Medintz IL, Hildebrandt N, and Miller LW. Time-gated FRET nanoassemblies for rapid and sensitive intra- and extracellular fluorescence imaging. Sci Adv, 2016. 2(6): e1600265.

de Bruin RC, Lougheed SM, van der Kruk L, Stam AG, Hooijberg E, Roovers RC, van Bergen En Henegouwen PM, Verheul HM, de Gruijl TD, and van der Vliet HJ. Highly specific and potently activating Vgamma9Vdelta2-T cell specific nanobodies for diagnostic and therapeutic applications. Clin Immunol, 2016. 169: 128-38.

Lameris R, de Bruin RC, van Bergen En Henegouwen PM, Verheul HM, Zweegman S, de Gruijl TD, and van der Vliet HJ. Generation and characterization of CD1d-specific single-domain antibodies with distinct functional features. Immunology, 2016. 149(1): 111-21.

van Driel PB, Boonstra MC, Slooter MD, Heukers R, Stammes MA, Snoeks TJ, de Bruijn HS, van Diest PJ, Vahrmeijer AL, van Bergen En Henegouwen PM, van de Velde CJ, Lowik CW, Robinson DJ, and Oliveira S. EGFR targeted nanobody-photosensitizer conjugates for photodynamic therapy in a pre-clinical model of head and neck cancer. J Control Release, 2016. 229: 93-105.

Broekgaarden M, van Vught R, Oliveira S, Roovers RC, van Bergen en Henegouwen PM, Pieters RJ, Van Gulik TM, Breukink E, and Heger M. Site-specific conjugation of single domain antibodies to liposomes enhances photosensitizer uptake and photodynamic therapy efficacy. Nanoscale, 2016. 8(12): 6490-4.

Kijanka MM, van Brussel AS, van der Wall E, Mali WP, van Diest PJ, van Bergen En Henegouwen PM, and Oliveira S. Optical imaging of pre-invasive breast cancer with a combination of VHHs targeting CAIX and HER2 increases contrast and facilitates tumour characterization. EJNMMI Res, 2016. 6(1): 14.

Kooijmans SA, Fliervoet LA, van der Meel R, Fens MH, Heijnen HF, van Bergen En Henegouwen PM, Vader P, and Schiffelers RM. PEGylated and targeted extracellular vesicles display enhanced cell specificity and circulation time. J Control Release, 2016. 224: 77-85.

van Brussel AS, Adams A, Oliveira S, Dorresteijn B, El Khattabi M, Vermeulen JF, van der Wall E, Mali WP, Derksen PW, van Diest PJ, and van Bergen En Henegouwen PM. Hypoxia-Targeting Fluorescent Nanobodies for Optical Molecular Imaging of Pre-Invasive Breast Cancer. Mol Imaging Biol, 2016. 18(4): 535-44.

2015

van Brussel AS, Adams A, Oliveira S, Dorresteijn B, El Khattabi M, Vermeulen JF, van der Wall E, Mali WP, Derksen PW, van Diest PJ, van Bergen En Henegouwen PM. Hypoxia-Targeting Fluorescent Nanobodies for Optical Molecular Imaging of Pre-Invasive Breast Cancer. Mol Imaging Biol. 2015 Nov 20. PubMed PMID:   26589824.

Mikhaylova M, Cloin BM, Finan K, van den Berg R, Teeuw J, Kijanka MM, Sokolowski M, Katrukha EA, Maidorn M, Opazo F, Moutel S, Vantard M, Perez F, van Bergen en Henegouwen PM, Hoogenraad CC, Ewers H, Kapitein LC. Resolving bundled microtubules using anti-tubulin nanobodies. Nat Commun. 2015 Aug 11;6:7933. doi: 10.1038/ncomms8933. PubMed PMID:   26260773.3.

Navis AC, van Lith SA, van Duijnhoven SM, de Pooter M, Yetkin-Arik B, Wesseling P, Hendriks WJ, Venselaar H, Timmer M, van Cleef P, van Bergen En Henegouwen P, Best MG, Wurdinger TD, Tops BB, Leenders WP. Identification of a novel MET mutation in high-grade glioma resulting in an auto-active intracellular protein. Acta Neuropathol. 2015 Apr 11. [Epub ahead of print] PubMed PMID: 25862637. 

Kijanka M, Dorresteijn B, Oliveira S, van Bergen en Henegouwen PM. Nanobody-based cancer therapy of solid tumors. Nanomedicine (Lond). 2015 Jan;10(1):161-74. doi: 10.2217/nnm.14.178. PubMed PMID: 25597775.

2014

Popov-Čeleketić D, van Bergen En Henegouwen PM. Membrane domain formation-a key factor for targeted intracellular drug delivery. Front Physiol. 2014 Dec 2;5:462. doi: 10.3389/fphys.2014.00462. eCollection 2014. Review. PubMed PMID: 25520666; PubMed Central PMCID: PMC4251288. 

Lameris R, de Bruin RC, Schneiders FL, van Bergen en Henegouwen PM, Verheul HM, de Gruijl TD, van der Vliet HJ. Bispecific antibody platforms for cancer immunotherapy. Crit Rev Oncol Hematol. 2014 Dec;92(3):153-65. doi: 10.1016/j.critrevonc.2014.08.003. Epub 2014 Aug 20. PubMed PMID: 25195094.

Hagemeijer MC, Monastyrska I, Griffith J, van der Sluijs P, Voortman J, van Bergen en Henegouwen PM, Vonk AM, Rottier PJ, Reggiori F, de Haan CA. Membrane rearrangements mediated by coronavirus nonstructural proteins 3 and 4. Virology.  2014 Jun;458-459:125-35. doi: 10.1016/j.virol.2014.04.027. Epub 2014 May 13. PubMed PMID: 24928045. 

Heukers R, van Bergen en Henegouwen PM, Oliveira S. Nanobody-photosensitizer conjugates for targeted photodynamic therapy. Nanomedicine. 2014 Oct;10(7):1441-51. doi: 10.1016/j.nano.2013.12.007. Epub 2014 Jan 3. PubMed PMID: 24394212. 

van Driel PB, van der Vorst JR, Verbeek FP, Oliveira S, Snoeks TJ, Keereweer S, Chan B, Boonstra MC, Frangioni JV, van Bergen en Henegouwen PM, Vahrmeijer AL, Lowik CW. Intraoperative fluorescence delineation of head and neck cancer with a  fluorescent anti-epidermal growth factor receptor nanobody. Int J Cancer. 2014 Jun 1;134(11):2663-73. doi: 10.1002/ijc.28601. Epub 2013 Dec 12. PubMed PMID: 24222574; PubMed Central PMCID: PMC3960332. 

Wegner KD, Lindén S, Jin Z, Jennings TL, el Khoulati R, van Bergen en Henegouwen PM, Hildebrandt N. Nanobodies and nanocrystals: highly sensitive quantum dot-based homogeneous FRET immunoassay for serum-based EGFR detection. Small. 2014 Feb 26;10(4):734-40. doi: 10.1002/smll.201302383. Epub 2013 Oct 2. PubMed PMID: 24115738.

Heukers R, Altintas I, Raghoenath S, De Zan E, Pepermans R, Roovers RC, Haselberg R, Hennink WE, Schiffelers RM, Kok RJ, and van Bergen en Henegouwen PM. Targeting hepatocyte growth factor receptor (Met) positive tumor cells using internalizing nanobody-decorated albumin nanoparticles. Biomaterials. 2014 Jan, 35(1): 601-10. PMID: 24139763.

2013

van Driel PB, van der Vorst JR, Verbeek FP, Oliveira S, Snoeks TJ, Keereweer S, Chan B, Boonstra MC, Frangioni JV, van Bergen En Henegouwen PM, Vahrmeijer AL, and Lowik CW. Intraoperative fluorescence delineation of head and neck cancer with a fluorescent Anti-epidermal growth factor receptor nanobody. Int J Cancer. 2013 Nov 13 PMID: 24222574.

Heukers R, Vermeulen JF, Fereidouni F, Bader AN, Voortman J, Roovers RC, Gerritsen HC, and van Bergen En Henegouwen PM. Endocytosis of EGFR requires its kinase activity and N-terminal transmembrane dimerization motif. J Cell Sci. 2013 Nov 1, 126(Pt 21): 4900-12. PMID: 23943881.

Kijanka M, Warnders FJ, El Khattabi M, Lub-de Hooge M, van Dam GM, Ntziachristos V, de Vries L, Oliveira S, and van Bergen En Henegouwen PM. Rapid optical imaging of human breast tumour xenografts using anti-HER2 VHHs site-directly conjugated to IRDye 800CW for image-guided surgery. Eur J Nucl Med Mol Imaging. 2013 Oct, 40(11): 1718-29. PMID: 23778558.

de Heus C, Kagie N, Heukers R, van Bergen en Henegouwen PM, and Gerritsen HC. Analysis of EGF receptor oligomerization by homo-FRET. Methods Cell Biol. 2013, 117: 305-21. PMID: 24143984.

van der Meel R, Oliveira S, Altintas I, Heukers R, Pieters EH, van Bergen en Henegouwen PM, Storm G, Hennink WE, Kok RJ, and Schiffelers RM. Inhibition of tumor growth by targeted anti-EGFR/IGF-1R nanobullets depends on efficient blocking of cell survival pathways. Mol Pharm. 2013 Oct 7, 10(10): 3717-27. PMID: 23889133.

Wegner KD, Linden S, Jin Z, Jennings TL, Khoulati RE, van Bergen En Henegouwen PM, and Hildebrandt N. Nanobodies and Nanocrystals: Highly Sensitive Quantum Dot-Based Homogeneous FRET Immunoassay for Serum-Based EGFR Detection. Small. 2013 Oct 2 PMID: 24115738.

van Brussel AS, Adams A, Vermeulen JF, Oliveira S, van der Wall E, Mali WP, van Diest PJ, and van Bergen En Henegouwen PM. Molecular imaging with a fluorescent antibody targeting carbonic anhydrase IX can successfully detect hypoxic ductal carcinoma in situ of the breast. Breast Cancer Res Treat. 2013 Jul, 140(2): 263-72. PMID: 23860929.

Schmitz KR, Bagchi A, Roovers RC, van Bergen en Henegouwen PM, and Ferguson KM. Structural evaluation of EGFR inhibition mechanisms for nanobodies/VHH domains. Structure. 2013 Jul 2, 21(7): 1214-24. PMID: 23791944.

Zaiss DM, van Loosdregt J, Gorlani A, Bekker CP, Grone A, Sibilia M, van Bergen en Henegouwen PM, Roovers RC, Coffer PJ, and Sijts AJ. Amphiregulin enhances regulatory T cell-suppressive function via the epidermal growth factor receptor. Immunity. 2013 Feb 21, 38(2): 275-84. PMID: 23333074.

Varkevisser R, Houtman MJ, Waasdorp M, Man JC, Heukers R, Takanari H, Tieland RG, van Bergen En Henegouwen PM, Vos MA, and van der Heyden MA. Inhibiting the clathrin-mediated endocytosis pathway rescues K(IR)2.1 downregulation by pentamidine. Pflugers Arch. 2013 Feb, 465(2): 247-59. PMID: 23192368.

Altintas I, Heukers R, van der Meel R, Lacombe M, Amidi M, van Bergen En Henegouwen PM, Hennink WE, Schiffelers RM, and Kok RJ. Nanobody-albumin nanoparticles (NANAPs) for the delivery of a multikinase inhibitor 17864 to EGFR overexpressing tumor cells. J Control Release. 2013 Jan 28, 165(2): 110-8. PMID: 23159529.

2012

van de Water JA, Bagci-Onder T, Agarwal AS, Wakimoto H, Roovers RC, Zhu Y, Kasmieh R, Bhere D, Van Bergen En Henegouwen PM, Shah K. Therapeutic stem cells expressing variants of EGFR-specific nanobodies have antitumor effects.  Proc Natl Acad Sci U S A. PMID: 23012408

Oliveira S, Cohen R, Stigter-van Walsum M, van Dongen GA, Elias SG, van Diest PJ, Mali W, van Bergen En Henegouwen PMP. A novel method to quantify IRDye800CW fluorescent antibody probes ex vivo in tissue distribution studies. EJNMMI Res. 2012 Sep 25;2(1):50. PMID: 23009555

van der Meel R, Oliveira S, Altintas I, Haselberg R, van der Veeken J, Roovers RC, van Bergen en Henegouwen PM, Storm G, Hennink WE, Schiffelers RM, Kok RJ. Tumor-targeted Nanobullets: Anti-EGFR nanobody-liposomes loaded with anti-IGF-1R kinase inhibitor for cancer treatment. J Control Release. 2012 Apr 30;159(2):281-9. PMID: 22227023

Oliveira S, van Dongen GA, Stigter-van Walsum M, Roovers RC, Stam JC, Mali W, van Diest PJ, van Bergen en Henegouwen PM. Rapid visualization of human tumor xenografts through optical imaging with a near-infrared fluorescent anti-epidermal growth factor receptor nanobody. Mol Imaging. 2012 Feb;11(1):33-46. PMID: 22418026

2011

Elstak ED, Neeft M, Nehme NT, Voortman J, Cheung M, Goodarzifard M, Gerritsen HC, van Bergen En Henegouwen PM, Callebaut I, de Saint Basile G, van der Sluijs P. The munc13-4-rab27 complex is specifically required for tethering secretory lysosomes at the plasma membrane. Blood. 2011 Aug 11;118(6):1570-8. PMID: 21693760

Low-Nam ST, Lidke KA, Cutler PJ, Roovers RC, van Bergen en Henegouwen PM, Wilson BS, Lidke DS. ErbB1 dimerization is promoted by domain co-confinement and stabilized by ligand binding. Nat Struct Mol Biol. 2011 Oct 23;18(11):1244-9. PMID:22020299

Emmerson CD, van der Vlist EJ, Braam MR, Vanlandschoot P, Merchiers P, de Haard HJ, Verrips CT, van Bergen en Henegouwen PM, Dolk E. Enhancement of polymeric immunoglobulin receptor transcytosis by biparatopic VHH. PLoS One. 2011;6(10):e26299. PMID:22022593

Roovers, R.C., Vosjan, M.W.J.D., Laeremans, T., de Bruin, R.C.G. Ferguson, K.M., . Verkleij, A.J., van Dongen, G.A.M.S., and van Bergen en Henegouwen, P.M.P. A bi-paratopic anti-EGFR nanobody efficiently inhibits solid tumour growth.  Int. J. Cancer

Oliveira1, S., van Dongen, G.A.M.S., Stigter-van Walsum, M., Roovers, R.C., Stam, J.C., Mali, W., van Diest, P.J., and van Bergen en Henegouwen, P.M.P. (2011) Rapid visualization of human tumor Xenografts through Optical Imaging with a Near infrared fluorescent anti-EGFR Nanobody. Molecular Imaging

Talelli, M., Rijcken, J.F., Oliveira, S., Van Meel, R., van Bergen en Henegouwen, P.M.P., Lammers, T., van Nostrum F., Storm, G. And Hennink, W.E. (2011) Nanobody – shell functionalized thermosensitive core-crosslinked polymeric micells for active drug targeting. Journal of Controlled Release. PMID: 21262289

Vosjan, M.J., Perk, L.R., Roovers, R.C., Visser, G.W.M., Stigter-van Walsum, M.,  van Bergen en Henegouwen, P.M.P. and van Dongen, G.A.M.S. (2011) Facile labeling of an anti-epidermal growth factor receptor Nanobody with Ga-68 via a novel bifunctional desferal chelate for immuno-PET. Eur J Nucl Med Mol Imaging. 2011 Jan 6. PMID: 21210114

2010-2006

2010

Hofman, E.G., Bader, A.N., Voortman, J., van den Heuvel, D., Verkleij, A.J., Gerritsen, H.C., and van Bergen en Henegouwen, P.M.P. (2010) Ligand-induced EGF receptor oligomerization is kinase-dependent and promotes internalization. J. Biol. Chem. 285: 39481-39489. PMID: 20940297

Oliveira, S., Schiffelers, R.M., van der Veeken, J.,van der Meel, R., Storm, G.,van Bergen en Henegouwen, P.M.P., and Roovers, R.C. (2010) Downregulation of EGFR by a novel multivalent nanobody-liposome platform Journal of Controlled Release 145; 145-175. PMID: 20362020

2009

Bader, A.N., Hofman, E.G., Voortman, J., van Bergen en Henegouwen, P.M.P., and Gerritsen, H.C. (2009) Homo-FRET imaging enables quantification of protein cluster sizes with sub-cellular resolution. Biophysical Journal. 97: 2613-2622. PMID: 19883605

Hofman, E,G, Bader, A.N., Gerritsen, H.C. and van Bergen en Henegouwen, P.M.P. (2009) EGF induces rapid reorganization of plasma membrane microdomains. Comm. & Integ. Biol. 2: 1-2. PMID: 19641732

Hamelers, I.H.L., Staffhorst, R.W.H.M., Voortman, J., de Kruijff, B., Reedijk, J., van Bergen en Henegouwen, P.M.P., and de Kroon, A.I.P.M.  (2009)  The high cytotoxicity of cisplatin nanocapsules in ovarian carcinoma cells depends on uptake by caveolae-mediated endocytosis. Clin. Cancer Res. 15: 1259-1268. PMID: 19228729

2008

Agronskaia, A.V., Valentijn; J.A., van Driel, L.F., Schneijdenberg, C., Humbel, B.M.,  van Bergen en Henegouwen, P.M.P., Verkleij, A.V., Koster, A.J.,. and Gerritsen, H. (2008). Integrated fluorescence and transmission electron microscopy. (2008) J. Struct Biol. 164; 183-189. PMID: 18664385

Hofman, E.G., Bader, A.N., Ruonala, M.O., van den Heuvel, D., Roovers, R.C., Verkleij, A.J., Gerritsen, H.C., and van Bergen en Henegouwen, P.M.P. (2008).  EGF induces coalescence of different lipid rafts. J. Cell Science 121: 2519-2528. PMID: 18628305

2007

Bader, A.N., Hofman, E.G., Van Bergen en Henegouwen, P.M.P., and Gerritsen, H.C. (2007) Imaging of protein cluster sizes by means of confocal time-gated fluorescence anisotropy microscopy. Optics Express 15: 6934-6945. PMID: 19547008

Sing, S., D’mello, V., van Bergen en Henegouwen, P.M.P. and Birge, R.B.. (2007) A NpxY-independent beta5 integrin activation signal regulates phagocytosis of apoptotic cells. Biochem. Biophys. Res. Commun. 364: 540-548. PMID: 17963729

Roovers, R.C., Laeremans, T., Huang, L., De Taeye, S., Verkleij, A.J., Revets, H., De Haard, H.J. and Van Bergen en Henegouwen, P.M.P. (2007) Efficient inhibition of EGFR signalling and of tumour growth by antagonistic anti-EGFR Nanobodies. Cancer Immunol. Immunoth. 56, 303-317. PMID: 16738850

2006

Fallon, L., Bélanger, C.M.L., Corera, A.T., Regan-Klapisz, E., Moreau, F., Voortman, J., Haber, M., Brice, A., Van Bergen en Henegouwen, P.M.P., and Fon, EA. ((2006) A regulated interaction with the UIM-protein Eps15 implicates parkin in EGF Receptor trafficking and signaling. Nature Cell Biology 8: 834-842. PMID: 16862145


Reviews:

Oliveira S, Heukers R, Sornkom J, Kok RJ, and van Bergen En Henegouwen PM. Targeting tumors with nanobodies for cancer imaging and therapy. J Control Release. 2013 Dec 28, 172(3): 607-17. PMID: 24035975.

Bader AN, Hoetzl S, Hofman EG, Voortman J, van Bergen en Henegouwen PMP, van Meer G, Gerritsen HC. (2010) Homo-FRET Imaging as a Tool to Quantify Protein and Lipid Clustering. Chemphyschem. PMID: 21344588

Van der Veeken, J., Oliveira, S., Schiffelers, R.M., Storm, G., Van Bergen en Henegouwen, P.M.P. and Roovers, R.C. (2009) Crosstalk between Epidermal growth factor receptor- and Insulin-like growth factor-1 receptor signaling: Implications for cancer therapy. Curr. Cancer drug targets 9: 748-760. PMID: 19754359

Van Bergen en Henegouwen, P.M.P. (2009) Eps15: a multifunctional adaptor protein regulating intracellular trafficking. Cell Comm. & Signaling 7: 24. PMID: 19814798

Roovers, R.C., van Dongen, G.A.M.S., and van Bergen en Henegouwen, P.M.P. (2007) Nanobodies in therapeutic applications.  Curr. Opin. Mol. Ther. 9:327-335. PMID: 17694445

Oliveira, S., van Bergen en Henegouwen, P.M.P., Storm, Schiffelers, R.M. (2006) Molecular Biology of EGFR Inhibition for Cancer Therapy. Exp. Opin. Biol. Ther. 6: 605-17. PMID: 16706607