Jeroen Bakkers

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

Silja Burkhard

PhD student
s.burkhard@hubrecht.eu

Silja Burkhard

Federico Tessadori

Postdoc
f.tessadori@hubrecht.eu

Federico Tessadori

Dennis de Bakker

PhD student
d.bakker@hubrecht.eu

dennisdebakker2

Sonja Chocron

Technician
s.chocron@hubrecht.eu

Sonja Chocron

Jeroen Bakkers

Group leader
j.bakkers@hubrecht.eu

bakkers

Fabian Kruse

PhD student
f.kruse@hubrecht.eu

Fabian Kruse

Melanie Laarman

PhD student
m.laarman@hubrecht.eu

Melanie Laarman

Laurence Garric

Postdoc
l.garric@hubrecht.eu

Laurence Garric

Sarah Kamel

PhD Student
s.kamel@hubrecht.eu

Sarah Maan Kamel

Sven Willekers

PhD student
s.willekers@hubrecht.eu

Sven Willekers

Lotte Koopman

PhD student
l.koopman@hubrecht.eu

Lotte

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More information

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In Februari 2015 Jeroen Bakkers has been appointed professor in Molecular Cardiogenetics at the University Medical Center. His inauguration took place Februari 3, 2016 in the Utrecht University Hall.

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2016-01-05_news-item_pic3

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.Paper_FKruse

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

Research

Bakkers_Islet1-5dpf-GFP-RFP-Whole

Bakkers: Cardiac Development and Genetics

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.

Read research

Key publications

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. Commun4:2754

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

All publications

Nodal signaling range is regulated by proprotein convertase-mediated maturation
2015 in Developmental Cell

Federico Tessadori, Emily S Noël, Elisabeth G Rens, Roberto Magliozzi, Inkie J A Evers-van Gogh, Daniele Guardavaccaro, Roeland M H Merks, Jeroen Bakkers

Animal and in silico models for the study of sarcomeric cardiomyopathies
2015 in Cardiovascular Research

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 zebrafish
2015 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 signaling
2015 in Development

Ina Strate, Federico Tessadori, Jeroen Bakkers

Recurrent Mutations in the Basic Domain of TWIST2 Cause Ablepharon Macrostomia and Barber-Say Syndromes
2015 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 Desminopathies
2015 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 Function
2015 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

Noonan and LEOPARD syndrome Shp2 variants induce heart displacement defects in zebrafish
2014 in Development

Monica Bonetti, Jeroen Paardekooper Overman, Federico Tessadori, Emily Noël, Jeroen Bakkers, Jeroen den Hertog

Mutations in SGOL1 cause a novel cohesinopathy affecting heart and gut rhythm
2014 in Nature Genetics

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

Genome-wide RNA Tomography in the zebrafish embryo
2014 in Cell

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

On the robustness of germ cell migration and microRNA-mediated regulation of chemokine signaling
2013 in Nature Genetics

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 formation
2013 in Trends in Cardiovascular Medicine

A.K. Lagendijk, A. Szabo, R.M. Merks, J. Bakkers

Ubiad1 is an antioxidant enzyme that regulates eNOS activity by CoQ10 synthesis
2013 in Cell

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

A Nodal-independent and tissue-intrinsic mechanism controls heart-looping chirality
2013 in Nature Communications

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 tissues
2012 in Biology open

A.K. Lagendijk, J.D. Moulton, J. Bakkers

Genetic variation in T-box binding element functionally affects SCN5A/SCN10A enhancer
2012 in Journal of Clinical Investigation

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 assembly
2012 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

Bmp signaling exerts opposite effects on cardiac differentiation
2012 in Circulation Research

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

Identification and regulation of a molecular module for bleb-based cell motility
2012 in Developmental Cell

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

Identification and functional characterization of cardiac pacemaker cells in zebrafish
2012 in PLoS One

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