Paul MP van Bergen en Henegouwen, PhD
Cell Biology, Science Faculty
Kruytgebouw, room N506
3584 CH Utrecht
Phone: +31-30-253 3349
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 the group of prof. Dr. H. Chap, ISERM Unit 326 in Toulouse, France, 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.
Our goal is to design molecules that are actively taken up by specific cells in vivo resulting in the intracellular delivery of imaging or therapeutic drugs. For this research we are combining different technologies in the field of Structural biology (X-ray and NMR), Bioinformatics, superresolution light microscopy, electron microscopy, animal imaging and antibody technology.
For the targeting of our molecules to specific cells we make use of antibody fragments generated from heavy chain antibodies that are present in animals from the camelidae family. These fragments consist of the variable fragment of the heavy chain (VHH) and are indicated as nanobodies or sDabs (single chain antibodies). Nanobodies have a molecular size of 15 kDa and can bind with high affinity to different targets. We select nanobodies by phage display and the selected nanobodies are functionalized by direct conjugation to fluorophores/toxins or nanoparticles using different strategies.
We are using nanobodies in our cell imaging studies for light- and electron microscopy, as novel anti-cancer therapeutics, and for in vivo imaging of tumor tissue. Receptor-mediated endocytosis into cells is done using bi-specific or bi-paratopic nanobodies. Because of their small size nanobodies have excellent penetration into tissues, which contributes to the rapid imaging of tumors and efficient treatment of cancer. Recently, bioinformatics was used to find tumor specific mutations leading to neo-antigens which can be used to generate personalized medicine.
Kaplan M, Narasimhan S, de Heus C, Mance D, van Doorn S, Houben K, Popov-Čeleketić D, Damman R, Katrukha E, Jain P, Geerts WJC, Heck AJR, Folkers G, Kapitein LC, Lemeer S, van Bergen en Henegouwen PMP and Baldus M. (2016) EGFR dynamics change during activation in native membranes as revealed by NMR. Cell. 2016 Nov 17;167(5):1241-1251. PMID: 27839865.
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. PMID: 26260773
Heukers R, Vermeulen JF, Fereidouni F, Bader AN, Voortman J, Roovers RC, Gerritsen HC, van Bergen En Henegouwen P.M.P. EGFR endocytosis 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, van Bergen En Henegouwen P.M.P. 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
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. 2012 Oct 9;109(41):16642-7. PMID: 23012408
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