Prof. dr. D.F.E. (Danny) Huylebroeck

Prof. Huylebroeck retired in June 2022 and has no active research group anymore.

Research

1. TGFβ family signalling in cell differentiation: from individual components to the family system

BMP signalling controls multiple cellular processes during embryogenesis and its developmental actions are recapitulated during tissue/organ repair. We study how these signals are interpreted within cells via co-operation of Smads and Smad-binding proteins, including transcription factors (TFs), serving the fine-tuning of the signalling and mounting proper and precise transcriptional responses in cell differentiation/maturation.

Our analysis of (primarily conditional) knockout (KO) mice combined with intense biochemistry/omics studies has over these many years revealed in vivo functions and action mechanisms of single components of the BMP system. However, cell-culture models are needed to study how the BMP system integrates into gene regulatory networks of cells, including stem/progenitor cells, and maintains cell-state or controls exit from (pluri)potency into entry/progression of differentiation, followed by cell maturation.

An overview of such regulations, including at the single-cell level, is missing for the BMP system. We have used perturbation (esiRNA) of a prioritized list of components and multi-omics read-out in stem cells, using mouse embryonic stem cells (mESCs) as main cell type. We integrated mRNA expression dynamics, gene-gene interactions inferred from these perturbations, and single-cell mRNA-profiling. Individual (esi-RNA based) perturbations reveal that the majority, i.e. 85%, of the 1,243 identified significant gene-gene interactions (of a theoretical total of 20,805) that we documented were restricted to one specific cell transition of cell stage, and are driven by a limited number of TFs.

Hence, the combination of profiling of temporal transcriptional changes, single-cell heterogeneity, and gene-gene interactions as assessed by individual perturbation, shows how intrinsically complex the transcriptional regulation within a given pathway is during cell transitions. The majority of gene-gene interactions remarkably display mainly cell-stage specific behavior. Therefore, the interpretation of the consequences of single-gene perturbation studies in cell lineage progression should occur with caution and consider cell stage and transition. Secondly, these results are to be considered in many of the CRISPR-KO based proposed improvements of tailored stem cells.

In addition, the single-cell RNA-profiling at each stage reveals the presence of subpopulations with stable co-expression modules, including of pluripotency genes in all stages. The fundamental questions here are to find out what the purpose of this is. Is this purely stochastic or is it maintenance of back-up pluripotency or, in general, is it plasticity? Furthermore, is this reduced, maintained or increased in BMP and/or Nodal-treated stem cells (e.g. ESCs submitted to mesendodermal cell differentiation)?

2. Multi-faceted functions and action modes of transcription factor Zeb2 in health and disease

Other studies in our group primarily address the multi-functional and multi-modal actions of the Mowat-Wilson Syndrome transcription factor ZEB2. Phenotypic analysis of conditional Zeb2 KO mice, combined with biochemistry/omics has revealed multiple functions and mechanisms of action of the Smad-interacting protein Zeb2. Altogether, these models explain major aspects of Mowat-Wilson Syndrome (MOWS, OMIM#235730), including intellectual disability (brain cortex development), epilepsy (GABAerigc interneurons in the ventral forebrain), Hirschsprung disease (neural crest, enteric nervous system) and other defects, including in neural crest derived craniofacial development. Additional mouse models studied in (often international) collaboration reveal hitherto unknown and sometimes unexpected functions in e.g. myelinogenesis and (re)myelination, maturation of subtypes of immune cell, and Zeb2-mediated cardiac repair attempts in the infarcted heart.

Our present work continues to study Zeb2 in neuronal and glial cells of the central and peripheral nervous systems, in neural differentiation of ESCs and iPSCs including from MOWS patients with new types of ZEB2 mutation and comparing the transcriptomes of the iPSCs under various differentiation protocols, also using cerebral organoids, and on Zeb2’s role in adult neurogenesis in the mouse brain.

We have identified Zeb2-dependent genes (RNA-Seq in Zeb2-KO cells) and novel protein partners (tag-Zeb2 proteomics), and are mapping Zeb2 genome-wide binding sites (ChIP-Seq) and post-translational modifications. Importantly, novel insights in Zeb2 locus regulation itself by distant regulatory elements, which are likely relevant to MOWS as well, were obtained by using targeted chromatin conformation capture (using the T2C approach). In addition to these studies, we would like to produce our own sets of genome-wide binding sites data for Smads in unstimulated and BMP/Nodal-stimulated ESCs, and compare these to Zeb2 binding sites, which will involve taking the cells to mesendodermal differentiation.

Some literature references covering this research:

Dries R, Stryjewska A, Coddens K, Okawa S, Notelaers T, Birkhoff J, Dekker M, Verfaillie CM, Del Sol Mesa A, Mulugeta E, Conidi A, Grosveld FG, Huylebroeck D. Integrative and perturbation based analysis of the transcriptional dynamics of the TGFβ/BMP signalling in transition from embryonic stem cells to neural progenitors. (2019). Stem Cells, in press.

Dobreva MP*, Escalona VA, Lawson KA, Sanchez MN, Ponomarev LC, Pereira PNG, Stryjewska A, Criem N, Huylebroeck D, Chuva de Sousa Lopes SM, Aerts S, Zwijsen A. (2018). Amniotic ectoderm expansion occurs via distinct modes and requires SMAD5-mediated signalling. Development 145, dev157222.

Stryjewska A, Dries R, Pieters T, Verstappen G, Conidi A, Coddens K, Francis A, Umans L, van IJcken WFJ, van Grunsven LA, Grosveld F, Goossens S, Haigh JJ, Huylebroeck D. (2017). Zeb2 regulates cell fate at the exit from epiblast state in mouse ESCs. Stem Cells35:611-625.

Wu LM, Wang J, Conidi A, Zhao C, Wang H, Ford Z, Zhang L, Zweier C, Ayee BG, Maurel P, Zwijsen A, Chan JR, Jankowski MP, Huylebroeck D, Lu RQ. (2016). Zeb2 recruits HDAC-NuRD to Inhibit Notch and controls Schwann cell differentiation and remyelination. Nat Neurosci. 19:1060-1072.

Scott CL, Soen B, Martens L, Skrypek N, Saelens W, Taminau J, Blancke G, Van Isterdael G, Huylebroeck D, Haigh J, Saeys Y, Guilliams M, Lambrecht B, Berx G. (2016). The transcription factor Zeb2 regulates development of conventional and plasmacytoid DCs by repressing Id2.  J Exp Med.213:897-911.

Gomes Fernandes M, Dries R, Roost MS, Semrau S, de Melo Bernardo A, Davis RP, Ramakrishnan R, Szuhai K, Maas E, Umans L, Abon Escalona V, Salvatori D, Deforce D, Van Criekinge W, Huylebroeck D, Mummery C, Zwijsen A, Chuva de Sousa Lopes SM. (2016). BMP-Smad signalling regulates lineage priming, but is dispensable for self-renewal in mouse embryonic stem cells. Stem Cell Reports 6, 85-94.

Van Helden MJ, Goossens S, Daussy C, Mathieu A-L, Faure F, Marçais A, Vandamme N, Farla N, Mayol K, Viel S, Degouve S, Debien E, Seuntjens E, Conidi A, Chaix J, Mangeot P, de Bernard S, Buffat L, Haigh JJ, Huylebroeck D, Lambrecht BN, Berx G, Walzer T. (2015). Terminal NK cell maturation is controlled by concerted actions of T-bet and Zeb2 and is essential for melanoma rejection.J Exp Med. 212, 2015-2025.

Omilusik KD, Best JA, Yu B, Goossens S, Weidemann A, Nguyen JV, Seuntjens E, Stryjewska A, Zweier C, Roychoudhuri R, Gattinoni L, Bird LM, Higashi Y, Kondoh H, Huylebroeck D, Haigh J, Goldrath AW. (2015). Transcriptional repressor ZEB2 promotes terminal differentiation of CD8+ effector and memory T cell populations during infection. J Exp Med. 212, 2027-2039.

van den Berghe V, Stappers E, Vandesande B, Dimidschstein J, Kroes R, Francis A, Conidi A, Lesage F, Dries R, Cazzola S, Berx G, Kessaris N, Vanderhaeghen P, van Ijcken W, Grosveld FG, Goossens S, Haigh JJ, Fishell G, Goffinet A, Aerts S, Huylebroeck D, Seuntjens E. (2013). Directed migration of cortical interneurons depends on the cell-autonomous action of Sip1. Neuron 77, 70-82.

Danny Huylebroeck studied zoology in Gent and obtained his PhD in molecular biology there (lab. Molecular Biology, director Walter Fiers), on the cloning and sequencing of the first human flu virus genes (in particular HA, NA), which explained the antigenic drift of the virus and the animal origin (in ducks) of the Hong Kong H3N2 virus 1968 pandemic. He was then EMBO post-doc fellow at the Cell Biology department at EMBL, Heidelberg, and worked on intracellular trafficking of membrane proteins, the cloning of infectious cDNA of the RNA-virus Semliki Forest Virus, and the cloning and expression of activin cDNA in mammalian cells.

After his return from EMBL, he became senior group leader at Innogenetics S.A. (INNX, Gent) and worked on growth factors, including on activins. In collaborations with the Hubrecht Laboratory, Utrecht, and MRC-NIMR, London, he demonstrated that activins had Spemann Organizer inducing activity in amphibian embryos, which was the true start for his further research in embryology.

In 1991 he established the new lab of Molecular Biology at KU Leuven with help of INNX (now Fujirebio). This academic lab, focusing on TGFβ/BMP signalling in vertebrate embryos and also developing new technologies, became part of the Flanders Institute of Biotechnology (VIB) in 1995 for 16 years. In 2006, he became full professor in developmental biology in the Faculty of Medicine and, in 2012, his lab became part of the new department of Development&Regeneration.

Mid-2013, he moved to the department of Cell Biology at Erasmus MC (Rotterdam), but also remained part-time affiliated to KU Leuven for research, teaching and coordination of multi-partner projects. Current research includes:

- Functional analysis of Smad signalling and Smad partners (transcription factors, e.g. ZEB2) in knockout mice and stem cells from mouse and human, including modeling Mowat-Wilson Syndrome.
- Systems biology of Smad/SIP signalling in embryonic stem cell differentiation.
- Mouse models for studying BMP and/or ZEB2 regulated stem cell niches.

Danny Huylebroeck retired from Erasmus MC in June 2022.

Publication list (from 2013 only)

van der PloegEK*, GolebskiK*, van Nimwegen M, FergussonJR, HeestersBA, Martinez-GonzalezI, KradolferCMA, van TolS, Scicluna BP, de BruijnMJW, de BoerGM, Tramper-StrandersGA, BraunstahlG-J, van IJckenWFJ, NagtegaalAP, van DrunenCM, FokkensWJ, HuylebroeckD, SpitsH, HendriksRW, Stadhouders R*,Bal SM*. Steroid-resistant human inflammatory ILC2s are marked by CD45RO and elevated in type 2 respiratory diseases. Sci Immunol. 6(55):eabd3489. https://pubmed.ncbi.nlm.nih.gov/33514640/

Gladka MM, Kohela A, Molenaar B, Versteeg D, Kooijman L, Monshouwer-Kloots J, Kremer V, Vos HR, Huibers MMH, Haigh JJ,  Huylebroeck D, Boon RA, Giacca M, van Rooij E*. (2020). Cardiomyocytes stimulate angiogenesis after ischemic injury in a ZEB2-dependent manner. Nat Commun., 12:84. https://pubmed.ncbi.nlm.nih.gov/33398012/

Groeneveldt LC, Herpelinck T, Maréchal M, Politis C, van IJcken WFJ, Huylebroeck D, Geris L*, Mulugeta E, Luyten FP. (2020). The bone-forming properties of periosteum-derived cells differ between harvest sites. Front Cell Dev Biol. 8:554984. https://pubmed.ncbi.nlm.nih.gov/33324630/

Menuchin-LasowskiY*, DaganB, ConidiA, Cohen-Gulkar M, DavidA, EhrlichM, Oren GiladiP, ClarkBS, BlackshawS, ShapiraK, HuylebroeckD, HenisY, Ashery-Padan Y*. (2020). Zeb2 regulates the balance between retinal interneurons and Muller glia by inhibition of BMP-Smad signaling. Dev Biol. 468: 80-92. https://pubmed.ncbi.nlm.nih.gov/32950463/

Boland BS*, He Z*, Tsai MS*, Olvera JG, Omilusik KD, Jin W, Duong HG, Kim ES, Limary AE, Jin W, Milner JJ, Yu B, Patel SA, Louis TL, Tysl T, Kurd NS, Bortnick A, Quezada LK, Kanbar JN, Miralles A, Huylebroeck D, Valasek MA, Dulai PS, Singh S, Lu L-F, Bui JD, Murre C, Sandborn WJ, Goldrath AW, Yeo GW*, Chang JT*. (2020). Heterogeneity and clonal relationships of adaptive immune cells in ulcerative colitis revealed by single-cell analyses. Sci Immunol., 5:Aug 21:eabb4432. doi: 10.1126/sciimmunol.abb4432. https://pubmed.ncbi.nlm.nih.gov/32826341/

Birkhoff JC, Brouwer RWW, Kolovos P, Korporaal AL, Bermejo-Santos A, Boltsis I, Nowosad K, van den Hout MCGN, Grosveld FG, van IJcken WFJ, Huylebroeck D*, Conidi A*. (2020). Targeted Chromatin Conformation (T2C) analysis identifies novel distal neural enhancers of ZEB2 in pluripotent stem cell differentiation. Hum Mol Genet.29: 2535-2550. https://pubmed.ncbi.nlm.nih.gov/32628253

Vandamme N*, Denecker G*, Bruneel K, Blancke G, Akay Ö, Taminau J, De Coninck J, De Smedt E, Skrypek N, Van Loocke W, Wouters J, Nittner D, Köhler C, Darling DS, Cheng P, Raaijmakers M, Levesque M, Girish Mallya U, Rafferty M, Balint B, Gallagher WM, Brochez L, Huylebroeck D, Haigh JJ, Andries V, Rambow F, Van Vlierberghe P, Goossens S, van den Oord J, Marine J-C, Berx G*. (2020). The EMT transcription factor ZEB2 promotes proliferation of primary and metastatic melanoma while suppressing an invasive, mesenchymal-like phenotype. Cancer Res. 80: 2983-2995. https://pubmed.ncbi.nlm.nih.gov/32503808

Di Filippo ES, Costamagna D, Giacomazzi G, Cortés-Calabuig A, Stryjewska A, Huylebroeck D, Fulle S, Sampaolesi M*. (2020). Zeb2 regulates myogenic differentiation in pluripotent stem cells. Int J Mol Sci. 21: E2525. https://www.ncbi.nlm.nih.gov/pubmed/32260521

Deryckere A^§, Stappers E^§, Dries R, Peyre E, van den Berghe V, Conidi A, Zampeta IF, Francis A, Bresseleers M, Stryjewska A, Vanlaer R, Maas E, Smal IV, van IJcken WFJ, Grosveld FG, Nguyen L, Huylebroeck D*, Seuntjens E*. (2020). Multifaceted actions of Zeb2 in postnatal neurogenesis from the V-SVZ to the olfactory bulb. Development 147:dev.184861. https://www.ncbi.nlm.nih.gov/pubmed/32253238

van Schoonhoven A, Huylebroeck D, Hendriks RW, Stadhouders R*. (2020). 3D genome organization during lymphocyte development and activation. Brief Funct Genomics 19: 71-82. https://www.ncbi.nlm.nih.gov/pubmed/31819944

Van der Ploeg EK, Carreras Mascaró A, Huylebroeck D, Hendriks RW, Stadhouders R*. (2020). Group 2 innate lymphoid cells in human respiratory disorders. J. Innate Immun. 12: 47-62. https://www.ncbi.nlm.nih.gov/pubmed/30726833

Dries R, Stryjewska A, Coddens K, Okawa S, Notelaers T, Birkhoff J, Dekker M, Verfaillie CM, Del Sol Mesa A, Mulugeta E, Conidi A, Grosveld FG, Huylebroeck D*. (2020). Integrative and perturbation based analysis of the transcriptional dynamics of the TGFβ/BMP signaling in transition from embryonic stem cells to neural progenitors. Stem Cells 38:202-217. https://www.ncbi.nlm.nih.gov/pubmed/31675135

Mfossa ACM, Thekkekara Puthenparampil H, Inalegwu A, Coolkens A, Baatout S, Benotmane MA, Huylebroeck D, Quintens R*. (2019). Exposure to ionizing radiation triggers prolonged changes in circular RNA expression in the embryonic mouse brain and primary neurons. Cells 8: 778. https://www.ncbi.nlm.nih.gov/pubmed/31357500

Van der Ploegh EK, Carreras Mascaró A, Huylebroeck D, Hendriks RW, Stadhouders R*. (2019). Group 2 innate lymphoid cells in human respiratory disorders. J. Innate Immun. Feb 6:1-16. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/30726833

Dobreva MP*, Escalona VA, Lawson KA, Sanchez MN, Ponomarev LC, Pereira PNG, Stryjewska A, Criem N, Huylebroeck D, Chuva de Sousa Lopes SM, Aerts S, Zwijsen A*. (2018). Amniotic ectoderm expansion occurs via distinct modes and requires SMAD5-mediated signalling. Development 145, dev157222. https://www.ncbi.nlm.nih.gov/pubmed/29884675

Giacomazzi G, Holvoet B, Trenson S, Caluwé E, Kravic B, Groosemans H, Cortes Calabuig Á, Deroose CM, Huylebroeck D, Hashemolhosseini S, Janssens S, McNally E, Quattrocelli M*, Sampaolesi M*. (2017). MicroRNAs promote skeletal muscle differentiation of mesodermal iPSC-derived progenitors. Nat Commun. 8:1249. https://www.ncbi.nlm.nih.gov/pubmed/29093487

Hegarty SV, Wyatt SL, Howard L, Stappers E, Huylebroeck D, Sullivan AM*, O’Keeffe GW*. (2017). Zeb2 is a negative regulator of midbrain dopaminergic axon growth and target innervation. Sci Rep. 7:8568. https://www.ncbi.nlm.nih.gov/pubmed/28819210

Watanabe Y⁺, Stanchina L⁺, Lecerf L, Gacem N, Conidi A, Baral V, Pingault V, Huylebroeck D, Bondurand N*. (2017). Differentiation of mouse enteric nervous system progenitor cells is controlled by Endothelin-3 and requires regulation of Ednrb by SRY-Box 10 and Zinc Finger E-Box Binding Homeobox 2. Gastroenterology 152:1139-1150. https://www.ncbi.nlm.nih.gov/pubmed/28063956

Stryjewska A*, Dries R*, Pieters T, Verstappen G, Conidi A, Coddens K, Francis A, Umans L, van IJcken WFJ, van Grunsven LA, Grosveld F, Goossens S, Haigh JJ, Huylebroeck D*. (2017). Zeb2 regulates cell fate at the exit from epiblast state in mouse ESCs. Stem Cells 35:611-625. https://www.ncbi.nlm.nih.gov/pubmed/27739137

Li J^§, Riedt T^§, Goossens S^§, Carrillo García C, Szczepanski S, Brandes M, Pieters T, Dobrosch L, Gütgemann I, Farla N, Radaelli E, Hulpiau P, Mallela N, Fröhlich H, La Starza R, Matteuci C, Chen T, Brossart P, Mecucci C, Huylebroeck D, Haigh JJ, Janzen V*. (2017). The EMT modulator Zeb2 regulates adult murine hematopoietic differentiation by regulating cytokine signalling. Blood 129:460-472. https://www.ncbi.nlm.nih.gov/pubmed/27683414

Menuchin-Lasowski Y, Oren-Giladi P, Xie Q, Ezra-Elia R, Ofri R, Peled-Hajaj S, Chen F, Higashi Y, Van de Putte T, Kondoh H, Huylebroeck D, Cvekl A, Ashery-Padan R*. (2016). Sip1/Zeb2 regulates the generation of the inner nuclear layer retinal cell lineages in mammals.Sip1/Zeb2 regulates the generation of the inner nuclear layer retinal cell lineages in mammals. Development 143:2829-2841. http://www.ncbi.nlm.nih.gov/pubmed/27385012

Beclin C*, Follert P*, Stappers E, Barral S, Coré N, Chevigny A, Magnone V, Lebrigand K, Bissels U, Huylebroeck D,Bosio A, Barbry P, Seuntjens E, Cremer H. (2016). miR-200 family controls late steps of postnatal forebrain neurogenesis via Zeb2 inhibition. Sci Rep. 6:35729 (with corrigendum 6:39368). https://www.ncbi.nlm.nih.gov/pubmed/27767083

Pieters T, Goosssens S, Haenebalcke L, Andries V, Stryjewska A, De Rycke R, Lemeire K, Hochepied T, Huylebroeck D, Berx G, Stemmler M, Wirth D, Haigh JJ, van Hengel J*, van Roy F*. (2016). p120 catenin-mediated stabilization of E-cadherin is essential for primitive endoderm specification. PLoS Genet. 12:e10006243. http://www.ncbi.nlm.nih.gov/pubmed/27556156

Quintes S^§, Brinkmann BG^§, Ebert M, Fröb F, Kungl T, Arlt FA, Tarabykin V, Huylebroeck D, Meijer D, Suter U, Wegner M, Sereda MW*, Nave K-A*. (2016). Zeb2 is essential for Schwann cell differentiation, myelination and nerve repair. Nat Neurosci. 19:1050-1059. http://www.ncbi.nlm.nih.gov/pubmed/27294512

Wu LM, Wang J, Conidi A, Zhao C, Wang H, Ford Z, Zhang L, Zweier C, Ayee BG, Maurel P, Zwijsen A, Chan JR, Jankowski MP, Huylebroeck D, Lu RQ*. (2016). Zeb2 recruits HDAC-NuRD to Inhibit Notch and controls Schwann cell differentiation and remyelination. Nat Neurosci. 19:1060-1072. http://www.ncbi.nlm.nih.gov/pubmed/27294509

Scott CL, Soen B, Martens L, Skrypek N, Saelens W, Taminau J, Blancke G, Van Isterdael G, Huylebroeck D, Haigh J, Saeys Y, Guilliams M, Lambrecht B*, Berx G*. (2016). The transcription factor Zeb2 regulates development of conventional and plasmacytoid DCs by repressing Id2. J Exp Med. 213:897-911. http://www.ncbi.nlm.nih.gov/pubmed/27185854

Costamagna D, Quattrocelli M, van Tienen F, Umans L, de Coo IFM, Zwijsen A, Huylebroeck D, Sampaolesi M*. (2016). Smad1/5/8 are myogenic regulators of murine and human mesoangioblasts. J Mol Cell Biol. 8:73-87. http://www.ncbi.nlm.nih.gov/pubmed/26450990

Borggrefe T*, Lauth M, Zwijsen A, Huylebroeck D, Herold S, Oswald F, Giaimo BD. (2016). The Notch intracellular domain integrates signals from Wnt, Hedgehog, BMP/TGFβ and hypoxia pathways. Biochim Biophys Acta - Mol Cell Res. 1863, 303-313. http://www.ncbi.nlm.nih.gov/pubmed/26592459

Gomes Fernandes M, Dries R, Roost MS, Semrau S, de Melo Bernardo A, Davis RP, Ramakrishnan R, Szuhai K, Maas E, Umans L, Abon Escalona V, Salvatori D, Deforce D, Van Criekinge W, Huylebroeck D, Mummery C, Zwijsen A, Chuva de Sousa Lopes SM*. (2016). BMP-Smad signalling regulates lineage priming, but is dispensable for self-renewal in mouse embryonic stem cells. Stem Cell Reports 6, 85-94. http://www.ncbi.nlm.nih.gov/pubmed/26711875

Van Helden MJ^, Goossens S^, Daussy C^, Mathieu A-L, Faure F, Marçais A, Vandamme N, Farla N, Mayol K, Viel S, Degouve S, Debien E, Seuntjens E, Conidi A, Chaix J, Mangeot P, de Bernard S, Buffat L, Haigh JJ, Huylebroeck D, Lambrecht BN, Berx G, Walzer T*. (2015). Terminal NK cell maturation is controlled by concerted actions of T-bet and Zeb2 and is essential for melanoma rejection. J Exp Med. 212, 2015-2025. http://www.ncbi.nlm.nih.gov/pubmed/26503444

Omilusik KD, Best JA, Yu B, Goossens S, Weidemann A, Nguyen JV, Seuntjens E, Stryjewska A, Zweier C, Roychoudhuri R, Gattinoni L, Bird LM, Higashi Y, Kondoh H, Huylebroeck D, Haigh J, Goldrath AW*. (2015). Transcriptional repressor ZEB2 promotes terminal differentiation of CD8+ effector and memory T cell populations during infection. J Exp Med. 212, 2027- 2039. http://www.ncbi.nlm.nih.gov/pubmed/26503445

Goossens S, Radaelli E, Blanchet O, Durinck K, Van der Meulen J, Peirs S, Taghon T, Tremblay C, Costa M, Ghahremani MF, De Medts J, Bartunkova S, Haigh K, Schwab C, Farla N, Pieters T, Matthijssens F, Van Roy N, Best JA, Deswarte K, Bogaert P, Carmichael C, Rickard A,  Suryani S, Bracken LS, Alserihi R, Canté-Barrett K, Haenebalcke L, Clappier E, RondouP, Slowicka L, Huylebroeck D, Goldrath AW, Janzen V, McCormack MP, Lock RB, Curtis D, Harrison C, Berx G, Speleman F, Meijerink JPP, SoulierJ, Van Vlierberghe P, Haigh JJ*. (2015). ZEB2 drives immature T-cell lymphoblastic leukemia development via enhanced tumor-initiating potential and IL-7 receptor signalling. Nat Commun. 6, 5794. http://www.ncbi.nlm.nih.gov/pubmed/25565005

INFRAFRONTIER Consortium - Meehan TF*, Chen C-K, Koscielny G, Relac M, Wilkinson P, Flicek P, Parkinson H, Castro A, Fessele S, Steinkamp R, Hagn M, Raess M, Hrabé de Angelis M, Bottomley J, Ramirez-Solis R, Smedley D, Ball S, Blake A, Fray M, Kenyon J, Mallon A-M, Brown S, Massimi M, Matteoni R, Tocchini-Valentini G, Herault Y, Kollias G, Ulfhake B,. Demengeot J, Fremond C, Bosch F, Montoliu L, Soininen R, Schughart K, Brakebusch C, Sedlacek R, Rülicke T, McKerlie C, Malissen B, Iraqi F, Jonkers J, Russig H, Huylebroeck D. (2015). INFRAFRONTIER: Providing mutant mouse resources as research tools for the international scientific community. Nucl Acids Res. 43 (Database issue):D1171-5. http://www.ncbi.nlm.nih.gov/pubmed/25414328

Giraud G, Stadhouders R, Conidi A, Dekkers DHW, Huylebroeck D, Demmers JAA, Soler E, Grosveld FG*. (2015). NLS-tagging: an alternative strategy to tag nuclear proteins. Nucl Acids Res. 43 (Database issue),D1171-11755. http://www.ncbi.nlm.nih.gov/pubmed/25260593

TatariMN, De CraeneB, TaminauJ, Vermassen P, GoossensS, HaighK, Cazzola S,Lambert J, HuylebroeckD, HaighJJ, BerxG*. (2014). ZEB2-transgene expression in the epidermis compromises the integrity of the epidermal barrier through the repression of different tight junction proteins. Cell Mol Life Sci. 71, 3599-3609. http://www.ncbi.nlm.nih.gov/pubmed/24573695

Denecker G, Vandamme N, Akay O, Koludrovic D, Taminau J, Lemeire K, Gheldof A, De Craene B, Van Gele M, Brochez L, Udupi GM, Rafferty M, Balint B, Gallagher WM, Ghanem G, Huylebroeck D, Haigh J, van den Oord J, Larue L, Davidson I, Marine J-C, Berx G*. (2014). Identification of a ZEB2-MITF-ZEB1 transcriptional network that controls melanogenesis and melanoma progression. Cell Death Differ. 21, 1250-1261. http://www.ncbi.nlm.nih.gov/pubmed/24769727

Lorès P, Vernet N, Kurosaki T, Van de Putte T, Huylebroeck D, Hikida M, Gacon G, Touré A*. (2013). Deletion of MgcRacGAP in the male germ cells impairs spermatogenesis and causes male sterility in the mouse. Dev Biol. 386, 419-427. http://www.ncbi.nlm.nih.gov/pubmed/24355749

Conidi A, van den Berghe V, Leslie K, Stryjewska A, Xue H, Chen Y-G, Seuntjens E, Huylebroeck D*. (2013). Four amino acids within a tandem QxVx repeat in a predicted α-helix of the Smad-binding domain of Sip1 are necessary for binding to activated Smad proteins. PLos One 8, e76733. http://www.ncbi.nlm.nih.gov/pubmed/24146916

Pradier B, Jeub M, Markert A, Mauer D, Tolksdorf K, Van de Putte T, Seuntjens E, Gailus-Durner V, Fuchs H, Hrabé de Angelis M, Huylebroeck D, Beck H, Zimmer A, Racz I*. (2013). Smad-interacting protein 1 affects acute and tonic, but not chronic pain Eur J Pain 18, 249-257. http://www.ncbi.nlm.nih.gov/pubmed/23861142

Conidi A, van den Berghe V, Huylebroeck D*. (2013). Aptamers and their potential to selectively target aspects of EGF, Wnt/β-catenin and TGFβ/Smad family signalling. Int J Mol Sci. 14, 6690-6719. http://www.ncbi.nlm.nih.gov/pubmed/23531534

Gomez-Herreros F, Romero-Granados R, Zeng Z, Alvarez-Quilon A, Quintero C, Ju L, Umans L, Vermeire L, Huylebroeck D, Caldecott KW*, Cortes-Ledesma*. (2013). TDP2-dependent non-homologous end-joining protects against topoisomerase II-induced DNA breaks and genome instability in cells and in vivo. PLoS Genetics 9, e1003226. http://www.ncbi.nlm.nih.gov/pubmed/23505375

Beets K, Huylebroeck D, Moya IM, Umans L, Zwijsen A*. (2013). Robustness in angiogenesis: Notch and BMP shaping waves. Trends Genet. 29, 140-149. http://www.ncbi.nlm.nih.gov/pubmed/23279848

McKinsey GL, Lindtner S, Trzcinski B, Visel A, Pennacchio LA, Huylebroeck D, Higashi Y, Rubenstein JL*. (2013). Dlx1&2-dependent expression of Zfhx1b (Sip1, Zeb2) regulates the fate switch between cortical and striatal interneurons. Neuron 77, 83-http://www.ncbi.nlm.nih.gov/pubmed/23312518

van den Berghe V, Stappers E, Vandesande B, Dimidschstein J, Kroes R, Francis A, Conidi A, Lesage F, Dries R, Cazzola S, Berx G, Kessaris N, Vanderhaeghen P, van Ijcken W, Grosveld FG, Goossens S, Haigh JJ, Fishell G, Goffinet A, Aerts S, Huylebroeck D*, Seuntjens E*. (2013). Directed migration of cortical interneurons depends on the cell-autonomous action of Sip1. http://www.ncbi.nlm.nih.gov/pubmed/23312517