Jeroen Bakkers received his PhD in 2000 from Leiden University, The Netherlands. During this time he was introduced in the zebrafish system and used it to study the role of glycosyltransferases during early vertebrate development. He continued his work on zebrafish development as a postdoc in the lab of Matthias Hammerschmidt at the Max-Planck Institute for Immunbiology in Freiburg, Germany. Here he started his work on Bmp and Wnt signaling during zebrafish gastrulation and isolated p63 (a member of the p53 tumor suppressor family) as a direct target of Bmp signalling. In 2003 he was appointed at the Hubrecht Institute initially as a junior staff member and in 2008 as a senior staff member and initiated here his work on heart development using zebrafish. In 2008 he was awarded a VIDI career grant from the Dutch science organization NWO and in 2015 he was appointed as Professor of Molecular Cardiogenetics at the UMC Utrecht.
j.bakkers(at)hubrecht.eu Send Mail
Team members Bakkers
Unlike humans, zebrafish are able to completely repair their heart after injury, for example a myocardial infarction-like event. But how is the fish able to regenerate this injury and, more specifically, what are the initial factors are that push heart muscle cells to start dividing again in order to replace the lost tissue.
To address this question, we developed a new method in the Bakkers group called tomo-seq. Applied to the regenerating heart, it allows us to obtain whole-genome expression data coupled with spatial resolution. This means, that we are able to find out which genes are expressed in which region along the axis injury area – borderzone – uninjured/remote myocardium. To achieve this, the injured heart is sectioned across one axis and every single section is barcoded before RNA-sequencing. This allows tracing back transcripts to the section (and thus position in the tissue) from which they originated in order to identify genes that are upregulated in a specific region of the tissue.
Focusing on the borderzone, which is known to house the majority of proliferating heart muscle cells, we found that bone morphogenetic protein (BMP) signalling is upregulated. BMP signaling has not been described to be involved in fish heart regeneration so far, and further experiments showed that knock-down of BMP resulted in fewer proliferating heart muscle cells. On the other hand, when BMP signalling was experimentally upregulated, more heart muscle cells started to divide, in turn increasing the regenerative potential.
In summary, we showed that spatially restricted gene expression can be identified with the tomo-seq method and that this can lead to the discovery of novel pathways involved in driving the regenerative process, like BMP signalling. Once we fully understand how regeneration occurs in the fish heart, we might be able to extrapolate these findings to humans in order to treat heart disease.
Spatially Resolved Genome-wide Transcriptional Profiling Identifies BMP Signaling as Essential Regulator of Zebrafish Cardiomyocyte Regeneration, Kruse, F*, Wu, C-C*,…Bakkers, J., Developmental Cell, 2016. *these authors contributed equally
Wide ranges of cardiac diseases are caused by genetic alterations, which affect normal cardiac development or function. The Bakkers' lab uses the zebrafish model to identify genes and mechanisms that regulate normal heart development, function and regeneration. In addition to better understand the genetics of cardiac diseases we study the effects of patient specific genetic variations in zebrafish. The projects in the lab use a wide range of approaches including reverse- and forward genetics, cell biology, mathematics and bioinformatics.
All publications can be found on research gate.
Wu, C.-C., Kruse, F., Vasudevarao, M. D., Junker, J. P., Zebrowski, D. C., Fischer, K., Bakkers, J. Spatially Resolved Genome-wide Transcriptional Profiling Identifies BMP Signaling as Essential Regulator of Zebrafish Cardiomyocyte Regeneration. Dev. Cell, 36(1), 36–49. doi:10.1016/j.devcel.2015.12.010
Tessadori, F., Noël, E.S., Rens, E.G., Magliozzi, R., Evers-van Gogh, I.J.A., Guardavaccaro, D., Merks, R.M.H. and Bakkers, J. Nodal signalling range is regulated by proprotein convertase-mediated secretion. Dev. Cell, doi:10.1016/j.devcel.2014.12.014
Junker, J.P.*, Noël, E.S*., Guryev, V., Peterson, K.A., Shah, G., Huisken, J., McMahon, A.P., Berezikov, E., Bakkers, J*. and van Oudenaarden, A.* (2014) Genome-wide RNA tomography in the zebrafish embryo. Cell159(3): 662-675
Chetaille, P.*, Côté, j.*, Burkhard, S.*, Houde, C., Preuss, C., Piché, J.,Gosset, N., Leclerc, S., Wünnemann, F., Cameron, M., Castilloux, J., Thibeault, M., Gagnon, C., Galli, A., Tuck, A., Hickson, G., Amine, N., Boufaied, I., Lemyre, E.,Santa Barbara, P., Faure, S., Jonzon, A., Dietz, H., Gallo-McFarlane, E., Benson, W., Zhan, S.H., Shen, Y., Jomphe, M., Jones, S.J.M., Bakkers, J., and Andelfinger, G.(2014) A human dysrhythmia syndrome affecting heart and gut is associated with mutations in SGOL1.Nat. Genet.46(11):1245-1249
Noël ES, Verhoeven M, Lagendijk AK, Tessadori F, Smith K, Choorapoikayil S, den Hertog J and Bakkers J. (2013) A Nodal-independent and tissue-intrinsic mechanism controls heart-looping chirality. Nat. Commun. 4:2754
Mugoni, V., Postel, R., Catanzaro, V., De Luca, E., Turco, E., Digilio, G., Silengo, Murphy, M.P., Medana, C., L., Stainier, D.Y.R., Bakkers, J. and Santoro, M.M. (2013) Ubiad1 Is an Antioxidant Enzyme that Regulates eNOS Activity by CoQ10 Synthesis. Cell 152; 504-518
Federico Tessadori, Emily S Noël, Elisabeth G Rens, Roberto Magliozzi, Inkie J A Evers-van Gogh, Daniele Guardavaccaro, Roeland M H Merks, Jeroen Bakkers
Dirk J Duncker, Jeroen Bakkers, Bianca J Brundel, Jeff Robbins, Jil C Tardiff, Lucie Carrier
GLUT12 deficiency during early development results in heart failure and a diabetic phenotype in zebrafish2015 in Journal of Endocrinology
Vanesa Jiménez-Amilburu, Susanne Jong-Raadsen, Jeroen Bakkers, Herman P Spaink, Rubén Marín-Juez
Glypican4 promotes cardiac specification and differentiation by attenuating canonical Wnt and Bmp signaling2015 in Development
Ina Strate, Federico Tessadori, Jeroen Bakkers
Recurrent Mutations in the Basic Domain of TWIST2 Cause Ablepharon Macrostomia and Barber-Say Syndromes2015 in American Journal of Human Genetics
Shannon Marchegiani, Taylor Davis, Federico Tessadori, Gijs van Haaften, Francesco Brancati, Alexander Hoischen, Haigen Huang, Elise Valkanas, Barbara Pusey, Denny Schanze, Hanka Venselaar, Anneke T Vulto-van Silfhout, Lynne A Wolfe, Cynthia J Tifft, Patricia M Zerfas, Giovanna Zambruno, Ariana Kariminejad, Farahnaz Sabbagh-Kermani, Janice Lee, Maria G Tsokos, Chyi-Chia R Lee, Victor Ferraz, Eduarda Morgana da Silva, Cathy A Stevens, Nathalie Roche, Oliver Bartsch, Peter Farndon, Eva Bermejo-Sanchez, Brian P Brooks, Valerie Maduro, Bruno Dallapiccola, Feliciano J Ramos, Hon-Yin Brian Chung, Cédric Le Caignec, Fabiana Martins, Witold K Jacyk, Laura Mazzanti, Han G Brunner, Jeroen Bakkers, Shuo Lin, May Christine V Malicdan, Cornelius F Boerkoel, William A Gahl, Bert B A de Vries, Mieke M van Haelst, Martin Zenker, Thomas C Markello
Developmental Alterations in Heart Biomechanics and Skeletal Muscle Function in Desmin Mutants Suggest an Early Pathological Root for Desminopathies2015 in Cell Reports
Caroline Ramspacher, Emily Steed, Francesco Boselli, Rita Ferreira, Nathalie Faggianelli, Stéphane Roth, Coralie Spiegelhalter, Nadia Messaddeq, Le Trinh, Michael Liebling, Nikhil Chacko, Federico Tessadori, Jeroen Bakkers, Jocelyn Laporte, Karim Hnia, Julien Vermot
A zebrafish Loss-of-Function Model for Human CFAP53 Mutations Reveals its Specific Role in Laterality Organ Function2015 in Human Mutation
Emily S Noël, Tarek S Momenah, Khalid Al-Dagriri, Abdulrahman Al-Suwaid, Safar Al-Shahrani, Hui Jiang, Sven Willekers, Yara Y Oostveen, Sonja Chocron, Alex V Postma, Zahurul A Bhuiyan, Jeroen Bakkers
Monica Bonetti, Jeroen Paardekooper Overman, Federico Tessadori, Emily Noël, Jeroen Bakkers, Jeroen den Hertog
Philippe Chetaille, Christoph Preuss, Silja Burkhard, Jean-Marc Côté, Christine Houde, Julie Castilloux, Jessica Piché, Natacha Gosset, Séverine Leclerc, Florian Wünnemann, Maryse Thibeault, Carmen Gagnon, Antonella Galli, Elizabeth Tuck, Gilles R Hickson, Nour El Amine, Ines Boufaied, Emmanuelle Lemyre, Pascal de Santa Barbara, Sandrine Faure, Anders Jonzon, Michel Cameron, Harry C Dietz, Elena Gallo-McFarlane, D Woodrow Benson, Claudia Moreau, Damian Labuda, Shing H Zhan, Yaoqing Shen, Michèle Jomphe, Steven J M Jones, Jeroen Bakkers, Gregor Andelfinger, FORGE Canada Consortium
Jan Philipp Junker, Emily S Noël, Victor Guryev, Kevin A Peterson, Gopi Shah, Jan Huisken, Andrew P McMahon, Eugene Berezikov, Jeroen Bakkers, Alexander van Oudenaarden
M. Goudarzi, I. Strate, A. Paksa, A.K. Lagendijk, J. Bakkers, E. Raz
Hyaluronan: a critical regulator of endothelial-to-mesenchymal transition during cardiac valve formation2013 in Trends in Cardiovascular Medicine
A.K. Lagendijk, A. Szabo, R.M. Merks, J. Bakkers
V. Mugoni, R. Postel, V. Catanzaro, E. De Luca, E. Turco, G. Digilio, L. Silengo, M.P. Murphy, C. Medana, D.Y. Stainier, J. Bakkers, M.M. Santoro
E.S. Noel, M. Verhoeven, A.K. Lagendijk, F. Tessadori, K. Smith, S. Choorapoikayil, J. den Hertog, J. Bakkers
Revealing details: whole mount microRNA in situ hybridization protocol for zebrafish embryos and adult tissues2012 in Biology open
A.K. Lagendijk, J.D. Moulton, J. Bakkers
M. van den Boogaard, L.Y. Wong, F. Tessadori, M.L. Bakker, L.K. Dreizehnter, V. Wakker, C.R. Bezzina, P.A. 't Hoen, J. Bakkers, P. Barnett, V.M. Christoffels
UDP-glucose dehydrogenase polymorphisms from patients with congenital heart valve defects disrupt enzyme stability and quaternary assembly2012 in Journal of Biological Chemistry
A.S. Hyde, E.L. Farmer, K.E. Easley, K. van Lammeren, V.M. Christoffels, J.J. Barycki, J. Bakkers, M.A. Simpson
E. de Pater, M. Ciampricotti, F. Priller, J. Veerkamp, I. Strate, K. Smith, A.K. Lagendijk, T.F. Schilling, W. Herzog, S. Abdelilah-Seyfried, M. Hammerschmidt, J. Bakkers
M. Goudarzi, T.U. Banisch, M.B. Mobin, N. Maghelli, K. Tarbashevich, I. Strate, J. ter Berg, H. Blaser, S. Bandemer, E. Paluch, J. Bakkers, I.M. Tolic-Norrelykke, E. Raz
F. Tessadori, J.H. van Weerd, S.B. Burkhard, A.O. Verkerk, E. de Pater, B.J. Boukens, A. Vink, V.M. Christoffels, J. Bakkers