Dr. N.J. (Niels) Galjart

Niels Galjart received his PhD in 1991 from the Erasmus MC, where he studied the molecular basis of the lysosomal storage disorder galactosialidosis. He did a postdoctoral training at the National Institute for Medical Research (London) from 1991-1993, and subsequently started his own research group at the Erasmus MC, where he has worked since. 

Lab members:

Sreya Basu (postdoc)
Nuo Yu (PhD student)
Lieke Stockman (PhD student)
Riccardo Viscusi (Technician)

Contact information

n.galjart@erasmusmc.nl

Erasmus MC
Dept. of Cell Biology
PO Box 2040
3000 CA  Rotterdam
The Netherlands

Visiting address: Dr Molewaterplein 40, 3015 GD - Ee building 10th floor, room Ee-1030

Cells in our body have particular shapes and form specialized tissues with defined functions. The microtubule (MT) cytoskeleton, a filamentous network that runs throughout cells, regulates cell shape and function by participating in many cellular processes. The perspective on MTs is often mechanical, as these polymers can function by exerting pushing and pulling forces, and also serve as railroad tracks for long-range intracellular transport. However, MTs are also implicated in cellular signalling, transcription and translation. We study the molecular mechanisms underlying the latter functions of MTs using in vitro, cellular and in vivo approaches. Our work has clinical relevance as MT-based processes are affected in a multitude of human diseases, and MTs are targets of important anti-cancer drugs.      

Research

Research in my lab is aimed at understanding mechanisms underlying cell structure and shape in health and disease. I focus on the role of the microtubule (MT) cytoskeleton and on a group of proteins, called MT plus-end tracking proteins (+TIPs), which specifically associate with the ends of growing MTs. I also study a nuclear factor, called CTCF, that organizes chromatin. Research in the last 5 years brings together these seemingly different subjects, as we are deciphering cytoplasmic interaction networks that coordinate signalling from the plasma membrane to the nucleus and back. Thus, we are slowly starting to understand the molecular players that link MT mechanics to signalling and transcription, and that ultimately regulate cell shape.

Recently my group developed a new approach to rapidly express and purify functional mammalian proteins. This allowed us to identify, for the first time, all tubulin associating proteins (the "tubulome") in HEK293 cells. Our results provide a resource for investigating tubulin interactions and functions, and reveal both tubulin-related disease mechanisms and new quality control systems that regulate MT behaviour and organization. I am using this cell and molecular biology expertise to develop clinical projects and to set up biotechnological platforms.

Ten selected publications (complete list of publications below)

(2012-2017)

Rosa-Garrido, M., Chapski, D.J., Schmitt, A.D., Kimball, T.H., Karbassi, E., Monte, E., Balderas, E., Pellegrini, M., Shih, T.T., Soehalim, E., Liem, D., Ping, P., Galjart, N.J., Ren, S., Wang, Y., Ren, B., and Vondriska, T.M. (2017). High-Resolution Mapping of Chromatin Conformation in Cardiac Myocytes Reveals Structural Remodeling of the Epigenome in Heart Failure. Circulation 136, 1613-1625. (PMID:28802249)

Perez-Garcia, A., Marina-Zarate, E., Alvarez-Prado, A.F., Ligos, J.M., Galjart, N., and Ramiro, A.R. (2017). CTCF orchestrates the germinal centre transcriptional program and prevents premature plasma cell differentiation. Nat Commun 8, 16067. (PMID:28677680)

Busslinger, G.A., Stocsits, R.R., van der Lelij, P., Axelsson, E., Tedeschi, A., Galjart, N., and Peters, J.M. (2017). Cohesin is positioned in mammalian genomes by transcription, CTCF and Wapl. Nature 544, 503-507. (PMID:28424523)

Yu, N., Signorile, L., Basu, S., Ottema, S., Lebbink, J.H., Leslie, K., Smal, I., Dekkers, D., Demmers, J., and Galjart, N. (2016). Isolation of Functional Tubulin Dimers and of Tubulin-Associated Proteins from Mammalian Cells. Curr Biol 26, 1728-1736. (PMID:27291054)

Basu, S., Sladecek, S., Martinez de la Pena y Valenzuela, I., Akaaboune, M., Smal, I., Martin, K., Galjart, N., and Brenner, H.R. (2015). CLASP2-dependent microtubule capture at the neuromuscular junction membrane requires LL5beta and actin for focal delivery of acetylcholine receptor vesicles. Mol Biol Cell 26, 938-951. (PMID:25589673)

van Haren, J., Boudeau, J., Schmidt, S., Basu, S., Liu, Z., Lammers, D., Demmers, J., Benhari, J., Grosveld, F., Debant, A., and Galjart, N. (2014). Dynamic Microtubules Catalyze Formation of Navigator-TRIO Complexes to Regulate Neurite Extension. Curr Biol 24, 1778-1785. (PMID:25065758)

Kim, L.K., Esplugues, E., Zorca, C.E., Parisi, F., Kluger, Y., Kim, T.H., Galjart, N.J., and Flavell, R.A. (2014). Oct-1 regulates IL-17 expression by directing interchromosomal associations in conjunction with CTCF in T cells. Mol Cell 54, 56-66. (PMID:24613343)

Sleutels, F., Soochit, W., Bartkuhn, M., Heath, H., Dienstbach, S., Bergmaier, P., Franke, V., Rosa-Garrido, M., van de Nobelen, S., Caesar, L., van der Reijden, M., Bryne, J.C., van Ijcken, W., Grootegoed, J.A., Delgado, M.D., Lenhard, B., Renkawitz, R., Grosveld, F., and Galjart, N. (2012). The male germ cell gene regulator CTCFL is functionally different from CTCF and binds CTCF-like consensus sites in a nucleosome composition-dependent manner. Epigenetics Chromatin 5, 8. (PMID:22709888)

Schmidt, N., Basu, S., Sladecek, S., Gatti, S., van Haren, J., Treves, S., Pielage, J., Galjart, N., and Brenner, H.R. (2012). Agrin regulates CLASP2-mediated capture of microtubules at the neuromuscular junction synaptic membrane. J Cell Biol 198, 421-437. (PMID:22851317)

Drabek, K., Gutierrez, L., Vermeij, M., Clapes, T., Patel, S.R., Boisset, J.C., van Haren, J., Pereira, A.L., Liu, Z., Akinci, U., Nikolic, T., van Ijcken, W., van den Hout, M., Meinders, M., Melo, C., Sambade, C., Drabek, D., Hendriks, R.W., Philipsen, S., Mommaas, M., Grosveld, F., Maiato, H., Italiano, J.E., Jr., Robin, C., and Galjart, N. (2012). The Microtubule Plus-End Tracking Protein CLASP2 Is Required for Hematopoiesis and Hematopoietic Stem Cell Maintenance. Cell Rep 2, 781-788. (PMID:23084744)

All publications

Rosa-Garrido, M., Chapski, D.J., Schmitt, A.D., Kimball, T.H., Karbassi, E., Monte, E., Balderas, E., Pellegrini, M., Shih, T.T., Soehalim, E., Liem, D., Ping, P., Galjart, N.J., Ren, S., Wang, Y., Ren, B., and Vondriska, T.M. (2017). High-Resolution Mapping of Chromatin Conformation in Cardiac Myocytes Reveals Structural Remodeling of the Epigenome in Heart Failure. Circulation 136, 1613-1625.

Perez-Garcia, A., Marina-Zarate, E., Alvarez-Prado, A.F., Ligos, J.M., Galjart, N., and Ramiro, A.R. (2017). CTCF orchestrates the germinal centre transcriptional program and prevents premature plasma cell differentiation. Nat Commun 8, 16067.

Gomez-Velazquez, M., Badia-Careaga, C., Lechuga-Vieco, A.V., Nieto-Arellano, R., Tena, J.J., Rollan, I., Alvarez, A., Torroja, C., Caceres, E.F., Roy, A.R., Galjart, N., Delgado-Olguin, P., Sanchez-Cabo, F., Enriquez, J.A., Gomez-Skarmeta, J.L., and Manzanares, M. (2017). CTCF counter-regulates cardiomyocyte development and maturation programs in the embryonic heart. PLoS Genet 13, e1006985.

Goldspink, D.A., Rookyard, C., Tyrrell, B.J., Gadsby, J., Perkins, J., Lund, E.K., Galjart, N., Thomas, P., Wileman, T., and Mogensen, M.M. (2017). Ninein is essential for apico-basal microtubule formation and CLIP-170 facilitates its redeployment to non-centrosomal microtubule organizing centres. Open Biol 7.

Busslinger, G.A., Stocsits, R.R., van der Lelij, P., Axelsson, E., Tedeschi, A., Galjart, N., and Peters, J.M. (2017). Cohesin is positioned in mammalian genomes by transcription, CTCF and Wapl. Nature 544, 503-507.

Yu, N., Signorile, L., Basu, S., Ottema, S., Lebbink, J.H., Leslie, K., Smal, I., Dekkers, D., Demmers, J., and Galjart, N. (2016). Isolation of Functional Tubulin Dimers and of Tubulin-Associated Proteins from Mammalian Cells. Curr Biol 26, 1728-1736.

Hernandez-Hernandez, A., Lilienthal, I., Fukuda, N., Galjart, N., and Hoog, C. (2016). CTCF contributes in a critical way to spermatogenesis and male fertility. Sci Rep 6, 28355.

Halim, D., Hofstra, R.M., Signorile, L., Verdijk, R.M., van der Werf, C.S., Sribudiani, Y., Brouwer, R.W., van, I.W.F., Dahl, N., Verheij, J.B., Baumann, C., Kerner, J., van Bever, Y., Galjart, N., Wijnen, R.M., Tibboel, D., Burns, A.J., Muller, F., Brooks, A.S., and Alves, M.M. (2016). ACTG2 variants impair actin polymerization in sporadic Megacystis Microcolon Intestinal Hypoperistalsis Syndrome. Hum Mol Genet 25, 571-583.

Remmelink, E., Loos, M., Koopmans, B., Aarts, E., van der Sluis, S., Smit, A.B., Verhage, M., and Neuro, B.M.P.C. (2015). A 1-night operant learning task without food-restriction differentiates among mouse strains in an automated home-cage environment. Behav Brain Res 283, 53-60.

Larti, F., Kahrizi, K., Musante, L., Hu, H., Papari, E., Fattahi, Z., Bazazzadegan, N., Liu, Z., Banan, M., Garshasbi, M., Wienker, T.F., Ropers, H.H., Galjart, N., and Najmabadi, H. (2015). A defect in the CLIP1 gene (CLIP-170) can cause autosomal recessive intellectual disability. Eur J Hum Genet 23, 331-336.

Basu, S., Sladecek, S., Martinez de la Pena y Valenzuela, I., Akaaboune, M., Smal, I., Martin, K., Galjart, N., and Brenner, H.R. (2015). CLASP2-dependent microtubule capture at the neuromuscular junction membrane requires LL5beta and actin for focal delivery of acetylcholine receptor vesicles. Mol Biol Cell 26, 938-951.

Weth, O., Paprotka, C., Gunther, K., Schulte, A., Baierl, M., Leers, J., Galjart, N., and Renkawitz, R. (2014). CTCF induces histone variant incorporation, erases the H3K27me3 histone mark and opens chromatin. Nucleic Acids Res 42, 11941-11951.

Watson, L.A., Wang, X., Elbert, A., Kernohan, K.D., Galjart, N., and Berube, N.G. (2014). Dual Effect of CTCF Loss on Neuroprogenitor Differentiation and Survival. J Neurosci 34, 2860-2870.

van Haren, J., Boudeau, J., Schmidt, S., Basu, S., Liu, Z., Lammers, D., Demmers, J., Benhari, J., Grosveld, F., Debant, A., and Galjart, N. (2014). Dynamic Microtubules Catalyze Formation of Navigator-TRIO Complexes to Regulate Neurite Extension. Curr Biol 24, 1778-1785.

Poulton, C.J., Schot, R., Seufert, K., Lequin, M.H., Accogli, A., Annunzio, G.D., Villard, L., Philip, N., de Coo, R., Catsman-Berrevoets, C., Grasshoff, U., Kattentidt-Mouravieva, A., Calf, H., de Vreugt-Gronloh, E., van Unen, L., Verheijen, F.W., Galjart, N., Morris-Rosendahl, D.J., and Mancini, G.M. (2014). Severe presentation of WDR62 mutation: is there a role for modifying genetic factors? Am J Med Genet A 164A, 2161-2171.

Nikolic, T., Movita, D., Lambers, M.E., Ribeiro de Almeida, C., Biesta, P., Kreefft, K., de Bruijn, M.J., Bergen, I., Galjart, N., Boonstra, A., and Hendriks, R. (2014). The DNA-binding factor Ctcf critically controls gene expression in macrophages. Cell Mol Immunol 11, 58-70.

Loos, M., Mueller, T., Gouwenberg, Y., Wijnands, R., van der Loo, R.J., Neuro, B.M.P.C., Birchmeier, C., Smit, A.B., and Spijker, S. (2014). Neuregulin-3 in the mouse medial prefrontal cortex regulates impulsive action. Biol Psychiatry 76, 648-655.

Kim, L.K., Esplugues, E., Zorca, C.E., Parisi, F., Kluger, Y., Kim, T.H., Galjart, N.J., and Flavell, R.A. (2014). Oct-1 regulates IL-17 expression by directing interchromosomal associations in conjunction with CTCF in T cells. Mol Cell 54, 56-66.

Basu, S., Sladecek, S., Pemble, H., Wittmann, T., Slotman, J.A., van Cappellen, W., Brenner, H.R., and Galjart, N. (2014). Acetylcholine receptor (AChR) clustering is regulated both by glycogen synthase kinase 3beta (GSK3beta)-dependent phosphorylation and the level of CLIP-associated protein 2 (CLASP2) mediating the capture of microtubule plus-ends. J Biol Chem 289, 30857-30867.

Zhao, X., Kumar, P., Shah-Simpson, S., Caradonna, K.L., Galjart, N., Teygong, C., Blader, I., Wittmann, T., and Burleigh, B.A. (2013). Host microtubule plus-end binding protein CLASP1 influences sequential steps in the Trypanosoma cruzi infection process. Cell Microbiol 15, 571-584.

Tortosa, E., Galjart, N., Avila, J., and Sayas, C.L. (2013). MAP1B regulates microtubule dynamics by sequestering EB1/3 in the cytosol of developing neuronal cells. Embo J 32, 1293-1306.

Ruiz-Saenz, A., van Haren, J., Laura Sayas, C., Rangel, L., Demmers, J., Millan, J., Alonso, M.A., Galjart, N., and Correas, I. (2013). Protein 4.1R binds to CLASP2 and regulates dynamics, organization and attachment of microtubules to the cell cortex. J Cell Sci 126, 4589-4601.

Leslie, K., and Galjart, N. (2013). Going solo: measuring the motions of microtubules with an in vitro assay for TIRF microscopy. Methods Cell Biol 115, 109-124.

Sleutels, F., Soochit, W., Bartkuhn, M., Heath, H., Dienstbach, S., Bergmaier, P., Franke, V., Rosa-Garrido, M., van de Nobelen, S., Caesar, L., van der Reijden, M., Bryne, J.C., van Ijcken, W., Grootegoed, J.A., Delgado, M.D., Lenhard, B., Renkawitz, R., Grosveld, F., and Galjart, N. (2012). The male germ cell gene regulator CTCFL is functionally different from CTCF and binds CTCF-like consensus sites in a nucleosome composition-dependent manner. Epigenetics Chromatin 5, 8.

Shih, H.Y., Verma-Gaur, J., Torkamani, A., Feeney, A.J., Galjart, N., and Krangel, M.S. (2012). Tcra gene recombination is supported by a Tcra enhancer- and CTCF-dependent chromatin hub. Proc Natl Acad Sci U S A.

Schmidt, N., Basu, S., Sladecek, S., Gatti, S., van Haren, J., Treves, S., Pielage, J., Galjart, N., and Brenner, H.R. (2012). Agrin regulates CLASP2-mediated capture of microtubules at the neuromuscular junction synaptic membrane. J Cell Biol 198, 421-437.

Loos, M., Staal, J., Pattij, T., Neuro, B.M.P.C., Smit, A.B., and Spijker, S. (2012). Independent genetic loci for sensorimotor gating and attentional performance in BXD recombinant inbred strains. Genes Brain Behav 11, 147-156.

Hirayama, T., Tarusawa, E., Yoshimura, Y., Galjart, N., and Yagi, T. (2012). CTCF Is Required for Neural Development and Stochastic Expression of Clustered Pcdh Genes in Neurons. Cell Rep 2, 345-357.

Drabek, K., Gutierrez, L., Vermeij, M., Clapes, T., Patel, S.R., Boisset, J.C., van Haren, J., Pereira, A.L., Liu, Z., Akinci, U., Nikolic, T., van Ijcken, W., van den Hout, M., Meinders, M., Melo, C., Sambade, C., Drabek, D., Hendriks, R.W., Philipsen, S., Mommaas, M., Grosveld, F., Maiato, H., Italiano, J.E., Jr., Robin, C., and Galjart, N. (2012). The Microtubule Plus-End Tracking Protein CLASP2 Is Required for Hematopoiesis and Hematopoietic Stem Cell Maintenance. Cell Rep 2, 781-788.

Ribeiro de Almeida, C., Stadhouders, R., de Bruijn, M.J., Bergen, I.M., Thongjuea, S., Lenhard, B., van Ijcken, W., Grosveld, F., Galjart, N., Soler, E., and Hendriks, R.W. (2011). The DNA-binding protein CTCF limits proximal Vkappa recombination and restricts kappa enhancer interactions to the immunoglobulin kappa light chain locus. Immunity 35, 501-513.

Jansen, R., Timmerman, J., Loos, M., Spijker, S., van Ooyen, A., Brussaard, A.B., Mansvelder, H.D., Neuro-Bsik Mouse Phenomics, C., Smit, A.B., de Gunst, M., and Linkenkaer-Hansen, K. (2011). Novel candidate genes associated with hippocampal oscillations. PLoS One 6, e26586.

van de Nobelen, S., Rosa-Garrido, M., Leers, J., Heath, H., Soochit, W., Joosen, L., Jonkers, I., Demmers, J., van der Reijden, M., Torrano, V., Grosveld, F., Delgado, M.D., Renkawitz, R., Galjart, N., and Sleutels, F. (2010). CTCF regulates the local epigenetic state of ribosomal DNA repeats. Epigenetics Chromatin 3, 19.

Stepanova, T., Smal, I., van Haren, J., Akinci, U., Liu, Z., Miedema, M., Limpens, R., van Ham, M., van der Reijden, M., Poot, R., Grosveld, F., Mommaas, M., Meijering, E., and Galjart, N. (2010). History-dependent catastrophes regulate axonal microtubule behavior. Curr Biol 20, 1023-1028.

Soshnikova, N., Montavon, T., Leleu, M., Galjart, N., and Duboule, D. (2010). Functional Analysis of CTCF During Mammalian Limb Development. Dev Cell 19, 819-830.

Lee, H.S., Komarova, Y.A., Nadezhdina, E.S., Anjum, R., Peloquin, J.G., Schober, J.M., Danciu, O., van Haren, J., Galjart, N., Gygi, S.P., Akhmanova, A., and Borisy, G.G. (2010). Phosphorylation controls autoinhibition of cytoplasmic linker protein-170. Mol Biol Cell 21, 2661-2673.

Galjart, N. (2010). Plus-end tracking proteins and their interactions at microtubule ends. Curr Biol 20, R528-R537.

Chang, J., Zhang, B., Heath, H., Galjart, N., Wang, X., and Milbrandt, J. (2010). Nicotinamide adenine dinucleotide (NAD)-regulated DNA methylation alters CCCTC-binding factor (CTCF)/cohesin binding and transcription at the BDNF locus. Proc Natl Acad Sci U S A.

Boisset, J.C., van Cappellen, W., Andrieu-Soler, C., Galjart, N., Dzierzak, E., and Robin, C. (2010). In vivo imaging of haematopoietic cells emerging from the mouse aortic endothelium. Nature 464, 116-120.

Watanabe, T., Noritake, J., Kakeno, M., Matsui, T., Harada, T., Wang, S., Itoh, N., Sato, K., Matsuzawa, K., Iwamatsu, A., Galjart, N., and Kaibuchi, K. (2009). Phosphorylation of CLASP2 by GSK-3beta regulates its interaction with IQGAP1, EB1 and microtubules. J Cell Sci 122, 2969-2979.

van Haren, J., Draegestein, K., Keijzer, N., Abrahams, J.P., Grosveld, F., Peeters, P.J., Moechars, D., and Galjart, N. (2009). Mammalian Navigators are microtubule plus-end tracking proteins that can reorganize the cytoskeleton to induce neurite-like extensions. Cell Motil Cytoskeleton 66, 824-838.

Ribeiro de Almeida, C., Heath, H., Krpic, S., Dingjan, G.M., van Hamburg, J.P., Bergen, I., van de Nobelen, S., Sleutels, F., Grosveld, F., Galjart, N., and Hendriks, R.W. (2009). Critical role for the transcription regulator CCCTC-binding factor in the control of Th2 cytokine expression. J Immunol 182, 999-1010.

Maffini, S., Maia, A.R., Manning, A.L., Maliga, Z., Pereira, A.L., Junqueira, M., Shevchenko, A., Hyman, A., Yates, J.R., 3rd, Galjart, N., Compton, D.A., and Maiato, H. (2009). Motor-independent targeting of CLASPs to kinetochores by CENP-E promotes microtubule turnover and poleward flux. Curr Biol 19, 1566-1572.

Zovko, S., Abrahams, J.P., Koster, A.J., Galjart, N., and Mommaas, A.M. (2008). Microtubule plus-end conformations and dynamics in the periphery of interphase mouse fibroblasts. Mol Biol Cell 19, 3138-3146.

Tanenbaum, M.E., Macurek, L., Galjart, N., and Medema, R.H. (2008). Dynein, Lis1 and CLIP-170 counteract Eg5-dependent centrosome separation during bipolar spindle assembly. Embo J 27, 3235-3245.

Smal, I., Meijering, E., Draegestein, K., Galjart, N., Grigoriev, I., Akhmanova, A., van Royen, M.E., Houtsmuller, A.B., and Niessen, W. (2008). Multiple object tracking in molecular bioimaging by Rao-Blackwellized marginal particle filtering. Med Image Anal 12, 764-777.

Smal, I., Draegestein, K., Galjart, N., Niessen, W., and Meijering, E. (2008). Particle filtering for multiple object tracking in dynamic fluorescence microscopy images: application to microtubule growth analysis. IEEE Trans Med Imaging 27, 789-804.

Patel-Hett, S., Richardson, J.L., Schulze, H., Drabek, K., Isaac, N.A., Hoffmeister, K., Shivdasani, R.A., Bulinski, J.C., Galjart, N., Hartwig, J.H., and Italiano, J.E., Jr. (2008). Visualization of microtubule growth in living platelets reveals a dynamic marginal band with multiple microtubules. Blood 111, 4605-4616.

Koning, R.I., Zovko, S., Barcena, M., Oostergetel, G.T., Koerten, H.K., Galjart, N., Koster, A.J., and Mieke Mommaas, A. (2008). Cryo electron tomography of vitrified fibroblasts: microtubule plus ends in situ. J Struct Biol 161, 459-468.

Hendriksen, J., Jansen, M., Brown, C.M., van der Velde, H., van Ham, M., Galjart, N., Offerhaus, G.J., Fagotto, F., and Fornerod, M. (2008). Plasma membrane recruitment of dephosphorylated beta-catenin upon activation of the Wnt pathway. J Cell Sci 121, 1793-1802.

Heimel, J.A., Hermans, J.M., Sommeijer, J.P., and Levelt, C.N. (2008). Genetic control of experience-dependent plasticity in the visual cortex. Genes Brain Behav 7, 915-923.

Heath, H., Ribeiro de Almeida, C., Sleutels, F., Dingjan, G., van de Nobelen, S., Jonkers, I., Ling, K.W., Gribnau, J., Renkawitz, R., Grosveld, F., Hendriks, R.W., and Galjart, N. (2008). CTCF regulates cell cycle progression of alphabeta T cells in the thymus. Embo J 27, 2839-2850.

Dragestein, K.A., van Cappellen, W.A., van Haren, J., Tsibidis, G.D., Akhmanova, A., Knoch, T.A., Grosveld, F., and Galjart, N. (2008). Dynamic behavior of GFP-CLIP-170 reveals fast protein turnover on microtubule plus ends. J Cell Biol 180, 729-737.

Tsvetkov, A.S., Samsonov, A., Akhmanova, A., Galjart, N., and Popov, S.V. (2007). Microtubule-binding proteins CLASP1 and CLASP2 interact with actin filaments. Cell Motil Cytoskeleton 64, 519-530.

Smal, I., Draegestein, K., Galjart, N., Niessen, W., and Meijering, E. (2007). Rao-Blackwellized marginal particle filtering for multiple object tracking in molecular bioimaging. Inf Process Med Imaging 20, 110-121.

Efimov, A., Kharitonov, A., Efimova, N., Loncarek, J., Miller, P.M., Andreyeva, N., Gleeson, P., Galjart, N., Maia, A.R., McLeod, I.X., Yates, J.R., 3rd, Maiato, H., Khodjakov, A., Akhmanova, A., and Kaverina, I. (2007). Asymmetric CLASP-dependent nucleation of noncentrosomal microtubules at the trans-Golgi network. Dev Cell 12, 917-930.

Wesoly, J., Agarwal, S., Sigurdsson, S., Bussen, W., Van Komen, S., Qin, J., van Steeg, H., van Benthem, J., Wassenaar, E., Baarends, W.M., Ghazvini, M., Tafel, A.A., Heath, H., Galjart, N., Essers, J., Grootegoed, J.A., Arnheim, N., Bezzubova, O., Buerstedde, J.M., Sung, P., and Kanaar, R. (2006). Differential contributions of mammalian Rad54 paralogs to recombination, DNA damage repair, and meiosis. Mol Cell Biol 26, 976-989.

van Horssen, R., Galjart, N., Rens, J.A., Eggermont, A.M., and ten Hagen, T.L. (2006). Differential effects of matrix and growth factors on endothelial and fibroblast motility: application of a modified cell migration assay. J Cell Biochem 99, 1536-1552.

Tanenbaum, M.E., Galjart, N., van Vugt, M.A., and Medema, R.H. (2006). CLIP-170 facilitates the formation of kinetochore-microtubule attachments. Embo J 25, 45-57.

Splinter, E., Heath, H., Kooren, J., Palstra, R.J., Klous, P., Grosveld, F., Galjart, N., and de Laat, W. (2006). CTCF mediates long-range chromatin looping and local histone modification in the beta-globin locus. Genes Dev 20, 2349-2354.

Peris, L., Thery, M., Faure, J., Saoudi, Y., Lafanechere, L., Chilton, J.K., Gordon-Weeks, P., Galjart, N., Bornens, M., Wordeman, L., Wehland, J., Andrieux, A., and Job, D. (2006). Tubulin tyrosination is a major factor affecting the recruitment of CAP-Gly proteins at microtubule plus ends. J Cell Biol 174, 839-849.

Pereira, A.L., Pereira, A.J., Maia, A.R., Drabek, K., Sayas, C.L., Hergert, P.J., Lince-Faria, M., Matos, I., Duque, C., Stepanova, T., Rieder, C.L., Earnshaw, W.C., Galjart, N., and Maiato, H. (2006). Mammalian CLASP1 and CLASP2 Cooperate to Ensure Mitotic Fidelity by Regulating Spindle and Kinetochore Function. Mol Biol Cell 17, 4526-4542.

Lansbergen, G., Grigoriev, I., Mimori-Kiyosue, Y., Ohtsuka, T., Higa, S., Kitajima, I., Demmers, J., Galjart, N., Houtsmuller, A.B., Grosveld, F., and Akhmanova, A. (2006). CLASPs attach microtubule plus ends to the cell cortex through a complex with LL5beta. Dev Cell 11, 21-32.

Drabek, K., van Ham, M., Stepanova, T., Draegestein, K., van Horssen, R., Sayas, C.L., Akhmanova, A., Ten Hagen, T., Smits, R., Fodde, R., Grosveld, F., and Galjart, N. (2006). Role of CLASP2 in Microtubule Stabilization and the Regulation of Persistent Motility. Curr Biol 16, 2259-2264.

Patel, S.R., Richardson, J.L., Schulze, H., Kahle, E., Galjart, N., Drabek, K., Shivdasani, R.A., Hartwig, J.H., and Italiano, J.E., Jr. (2005). Differential roles of microtubule assembly and sliding in proplatelet formation by megakaryocytes. Blood 106, 4076-4085.

Mimori-Kiyosue, Y., Grigoriev, I., Lansbergen, G., Sasaki, H., Matsui, C., Severin, F., Galjart, N., Grosveld, F., Vorobjev, I., Tsukita, S., and Akhmanova, A. (2005). CLASP1 and CLASP2 bind to EB1 and regulate microtubule plus-end dynamics at the cell cortex. J Cell Biol 168, 141-153.

Komarova, Y., Lansbergen, G., Galjart, N., Grosveld, F., Borisy, G.G., and Akhmanova, A. (2005). EB1 and EB3 Control CLIP Dissociation from the Ends of Growing Microtubules. Mol Biol Cell 16, 5334-5345.

Galjart, N. (2005). CLIPs and CLASPs and cellular dynamics. Nat Rev Mol Cell Biol 6, 487-498.

Burke, L.J., Zhang, R., Bartkuhn, M., Tiwari, V.K., Tavoosidana, G., Kurukuti, S., Weth, C., Leers, J., Galjart, N., Ohlsson, R., and Renkawitz, R. (2005). CTCF binding and higher order chromatin structure of the H19 locus are maintained in mitotic chromatin. Embo J 24, 3291-3300.

Akhmanova, A., Mausset-Bonnefont, A.L., van Cappellen, W., Keijzer, N., Hoogenraad, C.C., Stepanova, T., Drabek, K., van der Wees, J., Mommaas, M., Onderwater, J., van der Meulen, H., Tanenbaum, M.E., Medema, R.H., Hoogerbrugge, J., Vreeburg, J., Uringa, E.J., Grootegoed, J.A., Grosveld, F., and Galjart, N. (2005). The microtubule plus-end-tracking protein CLIP-170 associates with the spermatid manchette and is essential for spermatogenesis. Genes Dev 19, 2501-2515.

Lansbergen, G., Komarova, Y., Modesti, M., Wyman, C., Hoogenraad, C.C., Goodson, H.V., Lemaitre, R.P., Drechsel, D.N., Van Munster, E., Gadella, T.W., Jr., Grosveld, F., Galjart, N., Borisy, G.G., and Akhmanova, A. (2004). Conformational changes in CLIP-170 regulate its binding to microtubules and dynactin localization. J Cell Biol 166, 1003-1014.

Hoogenraad, C.C., Akhmanova, A., Galjart, N., and De Zeeuw, C.I. (2004). LIMK1 and CLIP-115: linking cytoskeletal defects to Williams syndrome. Bioessays 26, 141-150.

De Zeeuw, C.I., Koekkoek, S.K.E., van Alphen, A., Luo, C., Hoebeek, F., van der Steen, J., Frens, M.A., Sun, J., Goosens, H.H.L.M., Jaarsma, D., Coesmans, M.P.H., Schmolesky, M.T., De Jeu, M.T.G., and Galjart, N. (2004). Gain and phase control of compensatory eye movements by the flocculus of the vestibulocerebellum. In The vestibular system, S.M. Highstein, R.R. Fay, and A.N. Popper, eds. (New York Berlin Heidelberg, Springer-Verlag), pp. 375-422.

Stepanova, T., Slemmer, J., Hoogenraad, C.C., Lansbergen, G., Dortland, B., De Zeeuw, C.I., Grosveld, F., Van Cappellen, G., Akhmanova, A., and Galjart, N. (2003). Visualization of Microtubule Growth in Cultured Neurons via the Use of EB3-GFP (End-Binding Protein 3-Green Fluorescent Protein). J Neurosci 23, 2655-2664.

Hoogenraad, C.C., Wulf, P., Schiefermeier, N., Stepanova, T., Galjart, N., Small, J.V., Grosveld, F., De Zeeuw, C.I., and Akhmanova, A. (2003). Bicaudal D induces selective dynein-mediated microtubule minus end-directed transport. Embo J 22, 6004-6015.

Galjart, N., and Perez, F. (2003). A plus-end raft to control microtubule dynamics and function. Curr Opin Cell Biol 15, 48-53.

Matanis, T., Akhmanova, A., Wulf, P., Del Nery, E., Weide, T., Stepanova, T., Galjart, N., Grosveld, F., Goud, B., De Zeeuw, C.I., Barnekow, A., and Hoogenraad, C.C. (2002). Bicaudal-D regulates COPI-independent Golgi-ER transport by recruiting the dynein-dynactin motor complex. Nat Cell Biol 4, 986-992.

Komarova, Y.A., Akhmanova, A.S., Kojima, S., Galjart, N., and Borisy, G.G. (2002). Cytoplasmic linker proteins promote microtubule rescue in vivo. J Cell Biol 159, 589-599.

Hoogenraad, C.C., Koekkoek, B., Akhmanova, A., Krugers, H., Dortland, B., Miedema, M., Van Alphen, A., Kistler, W.M., Jaegle, M., Koutsourakis, M., Van Camp, N., Verhoye, M., Van Der Linden, A., Kaverina, I., Grosveld, F., De Zeeuw, C.I., and Galjart, N. (2002). Targeted mutation of Cyln2 in the Williams syndrome critical region links CLIP-115 haploinsufficiency to neurodevelopmental abnormalities in mice. Nat Genet 32, 116-127.

Coquelle, F.M., Caspi, M., Cordelieres, F.P., Dompierre, J.P., Dujardin, D.L., Koifman, C., Martin, P., Hoogenraad, C.C., Akhmanova, A., Galjart, N., De Mey, J.R., and Reiner, O. (2002). LIS1, CLIP-170's key to the dynein/dynactin pathway. Mol Cell Biol 22, 3089-3102.

Hoogenraad, C.C., Akhmanova, A., Howell, S.A., Dortland, B.R., De Zeeuw, C.I., Willemsen, R., Visser, P., Grosveld, F., and Galjart, N. (2001). Mammalian Golgi-associated Bicaudal-D2 functions in the dynein-dynactin pathway by interacting with these complexes. Embo J 20, 4041-4054.

Akhmanova, A., Hoogenraad, C.C., Drabek, K., Stepanova, T., Dortland, B., Verkerk, T., Vermeulen, W., Burgering, B.M., De Zeeuw, C.I., Grosveld, F., and Galjart, N. (2001). Clasps are CLIP-115 and -170 associating proteins involved in the regional regulation of microtubule dynamics in motile fibroblasts. Cell 104, 923-935.

Hoogenraad, C.C., Akhmanova, A., Grosveld, F., De Zeeuw, C.I., and Galjart, N. (2000). Functional analysis of CLIP-115 and its binding to microtubules. J Cell Sci 113, 2285-2297.

Akhmanova, A., Verkerk, T., Langeveld, A., Grosveld, F., and Galjart, N. (2000). Characterisation of transcriptionally active and inactive chromatin domains in neurons. J Cell Sci 113, 4463-4474.

Vanden Heuvel, J.P., Holden, P., Tugwood, J., Ingle, C., Yen, W., Galjart, N., and Greenlee, W.F. (1998). Identification of a Novel Peroxisome Proliferator Responsive cDNA Isolated from Rat Hepatocytes as the Zinc-Finger Protein ZFP-37. Toxicol Appl Pharmacol 152, 107-118.

Payen, E., Verkerk, T., Michalovich, D., Dreyer, S.D., Winterpacht, A., Lee, B., De Zeeuw, C.I., Grosveld, F., and Galjart, N. (1998). The centromeric/nucleolar protein ZFP-37 may function to specify neuronal nuclear domains. J Biol Chem 273, 9099-9109.

Hoogenraad, C.C., Eussen, B.H.J., Langeveld, A., Van Haperen, R., Winterberg, S., Wouters, C.H., Grosveld, F., De Zeeuw, C.I., and Galjart, N. (1998). The murine CYLN2 gene: genomic organisation, chromosome localisation and comparison to the human gene that is located within the 7q11.23 Williams Syndrome critical region. Genomics 53, 348-358.

De Zeeuw, C.I., Simpson, J.I., Hoogenraad, C.C., Galjart, N., Koekkoek, S.K.E., and Ruigrok, T.J.H. (1998). Microcircuitry and function of the inferior olive. TINS 21, 391-400.

Koekkoek, S.K.E., Van Alphen, A.M., Van de Burg, J., Grosveld, F., Galjart, N., and De Zeeuw, C.I. (1997). Gain adaptation and phase dynamics of compensatory eye movements in mice. Genes and function 1, 175-190.

De Zeeuw, C.I., Hoogenraad, C.C., Goedknegt, E., Hertzberg, E., Neubauer, A., Grosveld, F., and Galjart, N. (1997). CLIP-115, a novel brain-specific cytoplasmic linker protein, mediates the localization of dendritic lamellar bodies. Neuron 19, 1187-1199.

Mazarakis, N., Michalovich, D., Karis, A., Grosveld, F., and Galjart, N. (1996). Zfp-37 is a member of the KRAB zinc finger gene family and is expressed in neurons of the developing and adult CNS. Genomics 33, 247-257.

Kleijer, W.J., Geilen, G.C., Janse, H.C., van Diggelen, O.P., Zhou, X.Y., Galjart, N.J., Galjaard, H., and d'Azzo, A. (1996). Cathepsin A deficiency in galactosialidosis: studies of patients and carriers in 16 families. Pediatr Res 39, 1067-1071.

Bonten, E.J., Galjart, N.J., Willemsen, R., Usmany, M., Vlak, J.M., and d'Azzo, A. (1995). Lysosomal protective protein/cathepsin A. Role of the "linker" domain in catalytic activation. J Biol Chem 270, 26441-26445.

Morreau, H., Galjart, N.J., Willemsen, R., Gillemans, N., Zhou, X.Y., and d'Azzo, A. (1992). Human lysosomal protective protein. Glycosylation, intracellular transport, and association with beta-galactosidase in the endoplasmic reticulum. J Biol Chem 267, 17949-17956.

Zhou, X.Y., Galjart, N.J., Willemsen, R., Gillemans, N., Galjaard, H., and d'Azzo, A. (1991). A mutation in a mild form of galactosialidosis impairs dimerization of the protective protein and renders it unstable. Embo J 10, 4041-4048.

Wiegant, J., Galjart, N.J., Raap, A.K., and d'Azzo, A. (1991). The gene encoding human protective protein (PPGB) is on chromosome 20. Genomics 10, 345-349.

Galjart, N.J., Morreau, H., Willemsen, R., Gillemans, N., Bonten, E.J., and d'Azzo, A. (1991). Human lysosomal protective protein has cathepsin A-like activity distinct from its protective function. J Biol Chem 266, 14754-14762.

Galjart, N.J., Gillemans, N., Meijer, D., and d'Azzo, A. (1990). Mouse "protective protein". cDNA cloning, sequence comparison, and expression. J Biol Chem 265, 4678-4684.

van der Horst, G.T., Galjart, N.J., d'Azzo, A., Galjaard, H., and Verheijen, F.W. (1989). Identification and in vitro reconstitution of lysosomal neuraminidase from human placenta. J Biol Chem 264, 1317-1322.

Morreau, H., Galjart, N.J., Gillemans, N., Willemsen, R., van der Horst, G.T., and d'Azzo, A. (1989). Alternative splicing of beta-galactosidase mRNA generates the classic lysosomal enzyme and a beta-galactosidase-related protein. J Biol Chem 264, 20655-20663.

Galjart, N.J., Gillemans, N., Harris, A., van der Horst, G.T., Verheijen, F.W., Galjaard, H., and d'Azzo, A. (1988). Expression of cDNA encoding the human "protective protein" associated with lysosomal beta-galactosidase and neuraminidase: homology to yeast proteases. Cell 54, 755-764.

Galjart, N.J., Sivasubramanian, N., and Federici, B.A. (1987). Plasmid location, cloning, and sequence analysis of the gene encoding a 27.3-kilodalton cytolytic protein from Bacillus thuringiensis subsp. morrisoni (PG-14). Curr Microbiol 16, 171-177.

Federici, B.A., Ibarra, J.E., Padua, L.E., Galjart, N.J., and Sivasubramanian, N. (1987). Parasporal body of mosquitocidal subspecies of Bacillus thuringiensis. Biotechnology in invertebrate pathology and cell culture, 115-131. 

Role of CLASPs in transcription

MT plus-end tracking proteins (+TIPs) associate with the ends of growing MTs to regulate their fate and interactions. CLASPs are special +TIPs, as they can interpret signalling cues from the environment to stabilize subsets of MTs. We have previously shown that knockout of the Clasp2 gene leads to transcriptional defects in hematopoietic stem cells. More recent decent data reveal a role for CLASPs in transcription in embryonic stem cells and in the heart. Combined, our data suggest that CLASPs operate in feedback loops that affect the transcriptional output of cells. 

Tubulin: the building block

Back to basics: dissecting the fundamental mechanisms that regulate MT behaviour

Nuclear structure and chromatin organization

It is generally accepted that the architectural organisation of the nucleus and the regulation of transcription are functionally linked, but how this occurs is still unresolved. I am interested in describing constituents of nuclear and nucleolar chromatin that are involved in maintaining nuclear structure and organization. I focus my research on the multi-zinc finger transcription factors CTCF and its relative CTCFL, also called BORIS. CTCF is an eleven zinc finger (ZF) protein that demarcates chromatin domains, often by establishing DNA loops with cohesin. CTCF thereby regulates gene expression and epigenetic events. The function of the testis-specific protein CTCFL is less clear. We have generated various mutant cell and mouse lines of CTCF and CTCFL to study the function of these two interesting factors.