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 Immunobiology 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.
- Professor at Utrecht University
- Chairman at the Dutch Society of Developmental Biology
j.bakkers(at)hubrecht.eu Send Mail
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
A zebrafish Loss-of-Function Model for Human CFAP53 Mutations Reveals its Specific Role in Laterality Organ Function2016
Emily SNoël, Tarek SMomenah, KhalidAl-Dagriri, AbdulrahmanAl-Suwaid, SafarAl-Shahrani, HuiJiang, SvenWillekers, Yara YOostveen, SonjaChocron, Alex VPostma, Zahurul ABhuiyan, JeroenBakkers
BilgeSan, Naomi DChrispijn, NadineWittkopp, Simon Jvan Heeringen, Anne KLagendijk, MarcoAben, JeroenBakkers, René FKetting, Leonie MKamminga
Heterozygous KIDINS220/ARMS nonsense variants cause spastic paraplegia, intellectual disability, nystagmus, and obesity2016
Dragana JJosifova, Glen RMonroe, FedericoTessadori, Estherde Graaff, Bertvan der Zwaag, Sarju GMehta, MagdalenaHarakalova, Karen JDuran, Sanne M CSavelberg, Isaäc JNijman, HeinzJungbluth, Casper CHoogenraad, JeroenBakkers, Nine VKnoers, Helen VFirth, Philip LBeales, Gijsvan Haaften, Mieke Mvan Haelst, DDD Study
Spatially Resolved Genome-wide Transcriptional Profiling Identifies BMP Signaling as Essential Regulator of Zebrafish Cardiomyocyte Regeneration2016
Chi-ChungWu, FabianKruse, Mohankrishna DalvoyVasudevarao, Jan PhilippJunker, David CZebrowski, KristinFischer, Emily SNoël, DominicGrün, EugeneBerezikov, Felix BEngel, Alexandervan Oudenaarden, GilbertWeidinger, JeroenBakkers
GNB5 Mutations Cause an Autosomal-Recessive Multisystem Syndrome with Sinus Bradycardia and Cognitive Disability2016
Elisabeth MLodder, PasquelenaDe Nittis, Charlotte DKoopman, WojciechWiszniewski, Carolina FischingerMoura de Souza, NajimLahrouchi, NicolasGuex, ValerioNapolioni, FedericoTessadori, LeanderBeekman, Eline ANannenberg, LamiaeBoualla, Nico ABlom, Wimde Graaff, M.Kamermans, DarioCocciadiferro, NatasciaMalerba, BarbaraMandriani, Zeynep Hande CobanAkdemir, Richard JFish, Mohammad KEldomery, IlhamRatbi, Arthur A MWilde, Teunde Boer, William FSimonds, MargueriteNeerman-Arbez, V ReidSutton, FernandoKok, James RLupski, AlexandreReymond, Connie RBezzina, JeroenBakkers, GiuseppeMerla
FKruse, J PJunker, Avan Oudenaarden, JBakkers
Aimee D CPaulussen, AnjaSteyls, JoVanoevelen, Florence Hjvan Tienen, Ingrid P CKrapels, Godelieve RfClaes, SonjaChocron, CroolVelter, Gita MTan-Sindhunata, CatarinaLundin, IreneValenzuela, BalintNagy, IbenBache, Lisa LethMaroun, KristiinaAvela, Han GBrunner, Hubert J MSmeets, JeroenBakkers, Arthurvan den Wijngaard
Mitchell K LHan, EstebanHoijman, EmilyNöel, LaurenceGarric, JeroenBakkers, Johande Rooij
GNB5 Mutations Cause an Autosomal-Recessive Multisystem Syndrome with Sinus Bradycardia and Cognitive Disability2016
Elisabeth MLodder, PasquelenaDe Nittis, Charlotte DKoopman, WojciechWiszniewski, Carolina FischingerMoura de Souza, NajimLahrouchi, NicolasGuex, ValerioNapolioni, FedericoTessadori, LeanderBeekman, Eline ANannenberg, LamiaeBoualla, Nico ABlom, Wimde Graaff, MaartenKamermans, DarioCocciadiferro, NatasciaMalerba, BarbaraMandriani, Zeynep HandeCoban Akdemir, Richard JFish, Mohammad KEldomery, IlhamRatbi, Arthur A MWilde, Teunde Boer, William FSimonds, MargueriteNeerman-Arbez, V ReidSutton, FernandoKok, James RLupski, AlexandreReymond, Connie RBezzina, JeroenBakkers, GiuseppeMerla
FedericoTessadori, Emily SNoël, Elisabeth GRens, RobertoMagliozzi, Inkie J AEvers-van Gogh, DanieleGuardavaccaro, Roeland M HMerks, JeroenBakkers
Dirk JDuncker, JeroenBakkers, Bianca JBrundel, JeffRobbins, Jil CTardiff, LucieCarrier
GLUT12 deficiency during early development results in heart failure and a diabetic phenotype in zebrafish2015
VanesaJiménez-Amilburu, SusanneJong-Raadsen, JeroenBakkers, Herman PSpaink, RubénMarín-Juez
Glypican4 promotes cardiac specification and differentiation by attenuating canonical Wnt and Bmp signaling2015
InaStrate, FedericoTessadori, JeroenBakkers
Recurrent Mutations in the Basic Domain of TWIST2 Cause Ablepharon Macrostomia and Barber-Say Syndromes2015
ShannonMarchegiani, TaylorDavis, FedericoTessadori, Gijsvan Haaften, FrancescoBrancati, AlexanderHoischen, HaigenHuang, EliseValkanas, BarbaraPusey, DennySchanze, HankaVenselaar, Anneke TVulto-van Silfhout, Lynne AWolfe, Cynthia JTifft, Patricia MZerfas, GiovannaZambruno, ArianaKariminejad, FarahnazSabbagh-Kermani, JaniceLee, Maria GTsokos, Chyi-Chia RLee, VictorFerraz, Eduarda Morganada Silva, Cathy AStevens, NathalieRoche, OliverBartsch, PeterFarndon, EvaBermejo-Sanchez, Brian PBrooks, ValerieMaduro, BrunoDallapiccola, Feliciano JRamos, Hon-Yin BrianChung, CédricLe Caignec, FabianaMartins, Witold KJacyk, LauraMazzanti, Han GBrunner, JeroenBakkers, ShuoLin, May Christine VMalicdan, Cornelius FBoerkoel, William AGahl, Bert B Ade Vries, Mieke Mvan Haelst, MartinZenker, Thomas CMarkello
Developmental Alterations in Heart Biomechanics and Skeletal Muscle Function in Desmin Mutants Suggest an Early Pathological Root for Desminopathies2015
CarolineRamspacher, EmilySteed, FrancescoBoselli, RitaFerreira, NathalieFaggianelli, StéphaneRoth, CoralieSpiegelhalter, NadiaMessaddeq, LeTrinh, MichaelLiebling, NikhilChacko, FedericoTessadori, JeroenBakkers, JocelynLaporte, KarimHnia, JulienVermot
MonicaBonetti, JeroenPaardekooper Overman, FedericoTessadori, EmilyNoël, JeroenBakkers, Jeroenden Hertog
PhilippeChetaille, ChristophPreuss, SiljaBurkhard, Jean-MarcCôté, ChristineHoude, JulieCastilloux, JessicaPiché, NatachaGosset, SéverineLeclerc, FlorianWünnemann, MaryseThibeault, CarmenGagnon, AntonellaGalli, ElizabethTuck, Gilles RHickson, NourEl Amine, InesBoufaied, EmmanuelleLemyre, Pascalde Santa Barbara, SandrineFaure, AndersJonzon, MichelCameron, Harry CDietz, ElenaGallo-McFarlane, D WoodrowBenson, ClaudiaMoreau, DamianLabuda, Shing HZhan, YaoqingShen, MichèleJomphe, Steven J MJones, JeroenBakkers, GregorAndelfinger, FORGE Canada Consortium
Jan PhilippJunker, Emily SNoël, VictorGuryev, Kevin APeterson, GopiShah, JanHuisken, Andrew PMcMahon, EugeneBerezikov, JeroenBakkers, Alexandervan 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
A.K.Lagendijk, A.Szabo, R.M.Merks, J.Bakkers