Biomedical genomics

The architecture of DNA in the interior of the living cell nucleus is an emerging key contributor to genomic function. Aim of our research is to understand how genome structure influences genome function. We use and develop novel genomics approaches such as 4C technology to identify long-range DNA interactions, study gene regulation within and between mammalian chromosomes and uncover the proteins that dictate the shape of our genome. Besides transcription we study the impact of nuclear architecture on genomic rearrangements. Furthermore, we develop novel strategies to identify and map chromosomal aberrations.

Wouter de Laat

Wouter de Laat is group leader at the Hubrecht Institute and professor of Biomedical Genomics at University Medical Center Utrecht. His group develops and uses innovative high throughput technologies for optimized genetic diagnostics and to study the structure and function of our genome in health and disease.

  • Recipient of a prestigious VICI career grant in 2012
  • Founder and principal scientist of Cergentis (www.cergentis.com) since 2012
  • Professor of Biomedical Genomics at the University Medical Center Utrecht since 2009
  • Group leader at the Hubrecht Institute since 2008
  • Recipient of an ERC Young Investigator grant in 2008
  • Assistant professor (2004 – 2008) at the Erasmus University Rotterdam
  • Staff scientist (2000 – 2004) at the Erasmus University Rotterdam
  • Recipient of a prestigious VIDI career grant in 2000
  • Postdoc (1998 – 2000) working on beta-globin gene activation, in the group of Professor Frank Grosveld at the Erasmus University Rotterdam
  • PhD (1993 – 1998) working on the molecular mechanism of nucleotide excision repair, in the group of Professor Jan Hoeijmakers at the Erasmus University Rotterdam

 

Other activities

  • Professor at UMC Utrecht (Utrecht University)
  • Founder and shareholder at Cergentis
  • Member of the supervisory board at HUB (Hubrecht Organoid Technology)
  • Member of the scientific board at KWF

 

Contact
w.laat(at)hubrecht.eu
LinkedIn

Team membersde Laat

Luuk Peters

Student

Benjamin Maas

MSc Student

Valerio Bianchi

Postdoc

Mark Pieterse

Technician

Melissa van Kranenburg

Technician

Niels Rinzema

PhD Student

Erica Vos

PhD Student

Carlo Vermeulen

PhD Student

Carien Hilvering

PhD Student

Christian Valdes

Postdoc

Geert Geeven

Postdoc

Peter Krijger

Postdoc

Marjon Verstegen

Technician

Wouter de Laat

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Research

De Laat: Biomedical genomics

The architecture of DNA in the interior of the living cell nucleus is an emerging key contributor to genomic function. Aim of our research is to understand how genome structure influences genome function. We use and develop novel genomics approaches such as 4C technology to identify long-range DNA interactions, study gene regulation within and between mammalian chromosomes and uncover the proteins that dictate the shape of our genome. Besides transcription we study the impact of nuclear architecture on genomic rearrangements. Furthermore, we develop novel strategies to identify and map chromosomal aberrations.

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Key publications

de Vree PJP, de Wit E, Yilmaz M, van de Heijning M, Klous P, Verstegen MJAM, Wan Y, Teunissen H, Krijger PHL, Geeven G, Eijk PP, Sie D, Ylstra B, Hulsman LOM, van Dooren MF, van Zutven LJCM, van den Ouweland A, Verbeek S, van Dijk KW, Cornelissen M, Das AT, Berkhout B, Sikkema-Raddatz B, van den Berg E, van der Vlies P, Weening D, den Dunnen JT, Matusiak M, Lamkanfi M,  Ligtenberg MJL, ter Brugge P, Jonkers J, Foekens JA, Martens JW, van der Luijt R, Ploos van Amstel HK, van  Min M, Splinter E, de Laat W (2014). Targeted sequencing by proximity ligation for comprehensive variant detection and local haplotyping. Nature Biotechnology 32(10):1019-25.

de Laat W, Duboule D (2013). Topology of mammalian developmental enhancers and their regulatory landscapes. Nature 502(7472):499-506.

de Wit E, Bouwman BA, Zhu Y, Klous P, Splinter E, Verstegen MJ, Krijger PH, Festuccia N, Nora EP, Welling M, Heard E, Geijsen N, Poot RA, Chambers I, de Laat W. (2013) The pluripotent genome in three dimensions is shaped around pluripotency factors. Nature 501(7466):227-31.

van de Werken H, Landan G, Holwerda S, Hoichman M, Klous P, Chachik R, Splinter E, Valdes Quezada C, Öz Y, Bouwman B, Verstegen M, de Wit E, Tanay A, de Laat W. (2012). Robust 4C-seq data analysis to screen for regulatory DNA interactions. Nature Methods 9:969-72.

Noordermeer D#, de Wit E#, Klous P#, van de Werken H, Simonis M, Lopez-Jones M, Eussen B, de Klein A, Singer RH, de Laat W. (2011). Variegated gene expression caused by cell-specific long-range DNA interactions. Nat Cell Biol 13:944-51.
#equal contributions

Vermeulen C, Geeven G, de Wit W, Verstegen MJAM, Jansen RPM, van Kranenburg M, de Bruijn E, Pulit SL, Kruisselbrink E, Shahsavari Z, Omrani D, Zeinali F, Najmabadi H, Katsila T, Vrettou C, Patrinos GP, Traeger-Synodinos J, Splinter E, Beekman JM, Kheradmand K, te Meerman GJ, van Amstel HKP, de Laat W (2017). Sensitive Monogenic Noninvasive Prenatal Diagnosis by Targeted Haplotyping. American Journal of Human Genetics 101,1-14.

All publications

Regulation of disease-associated gene expression in the 3D genome
2016

Peter Hugo LodewijkKrijger, Wouterde Laat

Polarized regulatory landscape and Wnt responsiveness underlie Hox activation in embryos
2016 in22126

RoelNeijts, ShiluAmin, Carinavan Rooijen, SanderTan, Menno PCreyghton, Wouterde Laat, JacquelineDeschamps

The second decade of 3C technologies
2016 in22126

AnnetteDenker, Wouterde Laat

Cell-of-Origin-Specific 3D Genome Structure Acquired during Somatic Cell Reprogramming
2016 in6100153018

Peter Hugo LodewijkKrijger, BrunoDi Stefano, Elzode Wit, FrancescoLimone, Chrisvan Oevelen, Wouterde Laat, ThomasGraf

Epigenomic annotation of gene regulatory alterations during evolution of the primate brain
2016 in17436

Marit WVermunt, Sander CTan, BasCastelijns, GeertGeeven, PeterReinink, Ewartde Bruijn, IvanelaKondova, StephanPersengiev, RonaldBontrop, EdwinCuppen, Wouterde Laat, Menno PCreyghton, Netherlands Brain Bank

Cause and Consequence of Tethering a SubTAD to Different Nuclear Compartments
2016 in18606

Patrick JWijchers, Peter H LKrijger, GeertGeeven, YunZhu, AnnetteDenker, Marjon J A MVerstegen, ChristianValdes-Quezada, CarloVermeulen, MarkJanssen, HansTeunissen, Lisette C MAnink-Groenen, Pernette JVerschure, Wouterde Laat

Enhancers reside in a unique epigenetic environment during early zebrafish development
2016 in40944

Lucas J TKaaij, MichalMokry, MengZhou, MichaelMusheev, GeertGeeven, Adrien S JMelquiond, António Mde Jesus Domingues, Wouterde Laat, ChristofNiehrs, Andrew DSmith, René FKetting

Discovery and validation of sub-threshold genome-wide association study loci using epigenomic signatures
2016 in21100242814

XinchenWang, Nathan RTucker, GizemRizki, RobertMills, Peter HlKrijger, Elzode Wit, VidyaSubramanian, EricBartell, Xinh-XinhNguyen, JiangchuanYe, JordanLeyton-Mange, Elena VDolmatova, Pimvan der Harst, Wouterde Laat, Patrick TEllinor, ChristopherNewton-Cheh, David JMilan, ManolisKellis, Laurie ABoyer

Erratum to
2016 in40944

HendrikMarks, Hindrik H DKerstens, Tahsin StefanBarakat, ErikSplinter, René A MDirks, Guidovan Mierlo, OnkarJoshi, Shuang-YinWang, TomasBabak, Cornelis AAlbers, TüzerKalkan, AustinSmith, AliceJouneau, Wouterde Laat, JoostGribnau, Hendrik GStunnenberg

Transcription of Mammalian cis-Regulatory Elements Is Restrained by Actively Enforced Early Termination
2015 in18606

Liv M IAustenaa, IrosBarozzi, MartaSimonatto, SilviaMasella, GiuliaDella Chiara, SerenaGhisletti, AlessiaCurina, Elzode Wit, Britta A MBouwman, Stefanode Pretis, VivianaPiccolo, AlbertoTermanini, ElenaProsperini, MattiaPelizzola, Wouterde Laat, GioacchinoNatoli

CTCF Binding Polarity Determines Chromatin Looping
2015 in18606

Elzode Wit, Erica S MVos, Sjoerd J BHolwerda, ChristianValdes-Quezada, Marjon J A MVerstegen, HansTeunissen, ErikSplinter, Patrick JWijchers, Peter H LKrijger, Wouterde Laat

YAP Drives Growth by Controlling Transcriptional Pause Release from Dynamic Enhancers
2015 in18606

Giorgio GGalli, MatteoCarrara, Wei-ChienYuan, ChristianValdes-Quezada, BasantaGurung, BrianPepe-Mooney, TinghuZhang, GeertGeeven, Nathanael SGray, Wouterde Laat, Raffaele ACalogero, Fernando DCamargo

High-Affinity Sites Form an Interaction Network to Facilitate Spreading of the MSL Complex across the X Chromosome in Drosophila
2015 in18606

FidelRamírez, ThomasLingg, SarahToscano, Kin ChungLam, PlamenGeorgiev, Ho-RyunChung, Bryan RLajoie, Elzode Wit, YeZhan, Wouterde Laat, JobDekker, ThomasManke, AsifaAkhtar

A Long-Distance Chromatin Affair
2015 in18434

AnnetteDenker, Wouterde Laat

Architectural hallmarks of the pluripotent genome
2015 in17481

Britta A MBouwman, Wouterde Laat

Characterization and dynamics of pericentromere-associated domains in mice
2015 in22214

Patrick JWijchers, GeertGeeven, MichaelEyres, Atze JBergsma, MarkJanssen, MarjonVerstegen, YunZhu, YoriSchell, CarloVermeulen, Elzode Wit, Wouterde Laat

Genome-wide profiling of p53-regulated enhancer RNAs uncovers a subset of enhancers controlled by a lncRNA
2015 in19700182758

NicolasLéveillé, Carlos AMelo, KoosRooijers, AngelDíaz-Lagares, Sonia AMelo, GozdeKorkmaz, RuiLopes, FarhadAkbari Moqadam, Ana RMaia, Patrick JWijchers, GeertGeeven, Monique Lden Boer, RaghuKalluri, Wouterde Laat, ManelEsteller, ReuvenAgami

Getting the genome in shape
2015 in40944

Britta AmBouwman, Wouterde Laat

Dynamics of gene silencing during X inactivation using allele-specific RNA-seq
2015 in40944

HendrikMarks, Hindrik H DKerstens, Tahsin StefanBarakat, ErikSplinter, René A MDirks, Guidovan Mierlo, OnkarJoshi, Shuang-YinWang, TomasBabak, Cornelis AAlbers, TüzerKalkan, AustinSmith, AliceJouneau, Wouterde Laat, JoostGribnau, Hendrik GStunnenberg

Local compartment changes and regulatory landscape alterations in histone H1-depleted cells
2015 in40944

GeertGeeven, YunZhu, Byung JuKim, Boris ABartholdy, Seung-MinYang, Todd SMacfarlan, Wesley DGifford, Samuel LPfaff, Marjon J A MVerstegen, HugoPinto, Marit WVermunt, Menno PCreyghton, Patrick JWijchers, John AStamatoyannopoulos, Arthur ISkoultchi, Wouterde Laat