Research Groups

Genomic Instability in Development and Disease

‘Genomic instability leads to cells with an abnormal DNA content, i.e. aneuploid cells. As ageing is associated with the accumulation of aneuploid cells, genomic instability might explain why cancer occurs more frequently in the elderly.’

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  • Floris Foijer Visit
    Position

    Group Leader of the Laboratory of Genomic Instability in Development and Disease

    Research fields

    Mouse models for aneuploidy, spindle checkpoint, chromosomal instability, CIN, aneuploidy and cancer, aneuploidy and ageing

    Postdoctoral Fellows
    Maria Suarez Peredo Rodriquez
    PhD Students
    Andrea Tijhuis
    Anouk van den Brink
    Katya Dvorianinova
    Ruifang Tian
    Visit
    Siqi Zheng
    Soraya Wobben
    Xiao Ling
    Technicians
    Petra Bakker
    Mathilde Broekhuis
    Laura Kempe
    Rene Wardenaar

  • Chromosomal instability (CIN) is a hallmark feature of cancer. CIN leads to cells with an abnormal DNA content, a state known as aneuploidy affecting >80% of all cancers. Paradoxically, in untransformed cells, CIN and aneuploidy decrease cellular fitness and lead to activation of stress pathways. This suggests that cancer cells have found ways to cope with the downsides of CIN. A better understanding of these coping strategies can lead to new therapies that target these mechanisms, and thus selectively kill the aneuploid cancer cells with fewer side effects on healthy cells.

    In the Foijer lab, we study how cells deal with chromosomal instability and the resulting aneuploidy, in vitro as well as in vivo, to better understand what discriminates an aneuploid (cancer) cell from a normal cell. Importantly, we exploit our findings to design new strategies that selectively target aneuploid cells and collaborate with clinicians to translate our findings into clinical practice.

    The work in the lab focusses on four main themes:

    1) Development of technology and in vivo models to faithfully model and quantify chromosomal instability and aneuploidy

    2) Understanding how karyotype evolution shapes the genome of cancer cells

    3) Studies of the molecular mechanisms that discriminate aneuploid (cancer) cells from normal cells

    4) Efforts to exploit our mechanistic findings to design therapies that selectively kill cancer cells that display a CIN phenotype

     

    • Stroo E, Janssen L, Sin O, Hogewerf W, Koster M, Harkema L, Youssef SA, Beschorner N, Wolters AHG, Bakker B, Thathiah A, Foijer F, van de Sluis B, van Deursen J, Jucker M, de Bruin A, and Nollen EAA. (2023) Brain deletion of Serf2 shifts amyloid conformation in a mouse model. Life Science Alliance, in press
    • Spain L, Coulton A, Lobon I, Rowan A, Schnidrig D, Shepherd STC, Shum B, Byrne F, Goicoechea M, Piperni E, Au L, Edmonds K, Carlyle E, Hunter N, Renn A, Messiou C, Hughes P, Nobbs J, Foijer F, van den Bos H, Wardenaar R, Spierings DCJ, Spencer C, Schmitt AM, Tippu Z, Lingard K, Grostate L, Peat K, Kelly K, Sarker S, Vaughan S, Mangwende M, Terry L, Kelly D, Biano J, Murra A, Korteweg J, Lewis C, OFlaherty M, Cattin AL, Emmerich M, Gerard CL, Pallikonda HA, Lynch J, Mason R, Rogiers A, Xu H, Huebner A, McGranahan N, Al Bakir M, Murai J, Naceur-Lombardelli C, Borg E, Mitchison M, Moore DA, Falzon M, Proctor I, Stamp GWH, Nye EL, Young K, Furness AJS, Pickering L, Stewart R, Mahadeva U, Green A, Larkin J, Litchfield K, Swanton C, Jamal-Hanjani M, Turajlic S. (2023) Late-stage metastatic melanoma emerges through a diversity of evolutionary pathways. Cancer Discovery.  
    • Truong MY, Cané-Gasull P, de Vries SG, Nijenhuis W, Wardenaar R, Kapitein LC, Foijer F, Lens SMA (2023) A motor-based approach to induce chromosome-specific mis-segregations in human cells. EMBO Journal.
    • Woodward E, Yang M, Moura-Castro LH, van den Bos H, Gunnarsson R, Olsson-Arvidsson L, Spierings DCJ, Castor A, Duployez N, Zaliova M, Zuna J, Johansson B, Foijer F, Paulsson K (2023) Clonal origin and development of high hyperdiploidy in childhood acute lymphoblastic leukaemia. Nature Communication.  
    • De Feudis G, Garribba L, Martis V, Galli M, Dumont M, Eliezer Y, Wardenaar R, Ippolito MR, Iyer D.R, Tijhuis AE, Spierings DCJ, Schubert M, Rhind N, Foijer F, Ben-David U, Fachinetti D, Doksani Y. and Santaguida S. (2023) Molecular origins of genome instability following a single chromosome mis-segregation event. Nature Communication.        
    • Assoni AF, Foijer F, Zatz M. (2022) Amyotrophic Lateral Sclerosis, FUS and Protein Synthesis Defects. Stem Cell Rev Rep. Online ahead of print.
    • Mañas A, Aaltonen K, Andersson N, Hansson K, Adamska A, Seger A, Yasui H, Van den Bos H, Radke K, Esfandyari J, Lindgren D, Bhave M, Karlsson J, Spierings DCJ, Foijer F, Gisselsson D and Bexell D. (2022) Clinically-relevant treatment of PDX models reveals patterns of neuroblastoma chemoresistance. Science Advances
    • Mazzagatti A, Shaikh N, Bakker B, Spierings DCJ, Wardenaar R, Maniati R, Wang J, Boemo MA, Foijer F, McClelland SE. (2022) DNA Replication Stress Generates Distinctive Landscapes of DNA Copy Number Alterations and Chromosome Scale Losses. Genome Biology.  
    • Klaasen SJ,Truong MA, van Jaarsveld RH., Koprivec I,  Štimac V, de Vries S.G, Risteski P, Kodba S, Vukušić K, de Luca K, Marques JF, Gerrits EM, Bakker B, Foijer F, Kind J, Tolić IM, Lens SMA. and Kops GJPL.  Nuclear position of chromosomes dictates probability of missegregation and micronuclear entrapment. (2022) Nature.
    • Bockaj I, Martini TEI, Smit MJ, Armandari I, Bakker B, Wardenaar R, Meeuwsen- de Boer TGJ, Bakker PL, Spierings DCJ, Hoving EW, Guryev V, Foijer F and Bruggeman SWM. (2022) Chromosomal Instability Characterizes Pediatric Medulloblastoma but Is Not Tolerated in the Developing Cerebellum. International Journal of Medical Sciences.    
    • Hong C, Schubert M, Tijhuis AE, Requesens M, Roorda M, van den Brink A, Andrade Ruiz L, Bakker PL, van der Sluis T, Pieters W, Chen M, Wardenaar R, van der Vegt B, Spierings DCJ, de Bruyn M, van Vugt MATM, and Foijer F.(2022) IL6 signalling as a targetable vulnerability in chromosomally instable cancers. Nature.
    • Gemble S, Wardenaar R, Keuper K, Srivastava N, Nano M, Macé A, Tijhuis AE, Bernhard SV, Spierings DCJ, Simon A, Goundiam O, Hochegger H, Piel M, Foijer F, Storchová Z, and Basto R.(2022) Genetic instability from a single S-phase after whole genome duplication. Nature.
    • Eerkens AL, Vledder A, van Rooij N, Foijer F, Nijman HW,  de Bruyn M. (2022) Rapid and efficient generation of antigen-specific isogenic T cells from cryopreserved blood samples. Immunology & Cell Biology
    • Bočkaj I, Martini TEI, de Camargo Magalhães ES, Bakker PL, Meeuwsen-de Boer TGJ, Armandari I, Meuleman SL, Mondria MT, Stok C, Kok YP, Bakker B, Wardenaar R, Seiler J, Broekhuis MJC, van den Bos H, Spierings DCJ, Ringnalda FCA, Clevers H, Schüller U, van Vugt MATM, Foijer F, Bruggeman SWM.(2021) The H3.3K27M oncohistone affects replication stress outcome and provokes genomic instability in pediatric glioma. PLoS Genetics.
    • Coulson-Gilmer C, Morgan RD, Nelson L, Barnes BM, Tighe A, Wardenaar R, Spierings DCJ, Schlecht H, Burghel GJ, Foijer F, Desai S, McGrail JC, Taylor SS. (2021) Replication catastrophe is responsible for intrinsic PAR glycohydrolase inhibitor-sensitivity in patient-derived ovarian cancer models. Journal of Experimental & Clinical Cancer Research.
    • Bronder D, Tighe A, Wangsa D, Zong D, Meyer TJ, Wardenaar R, Minshall P, Hirsch D, Heselmeyer-Haddad K, Nelson L, Spierings D, McGrail JC, Cam M, Nussenzweig A, Foijer F, Ried T, Taylor SS.(2021) TP53 loss initiates chromosomal instability in fallopian tube epithelial cells. Disease Models & Mechanisms.
    • Zhou L, Zheng S, Bringas FRR, Bakker B, Simon JE, Bakker PL, Kazemier HG, Schubert M, Roorda M, van Vugt MATM, Chang M, Foijer F. (2021) A synthetic lethal screen identifies HDAC4 as a potential target in MELK overexpressing cancers. G3 (Bethesda).
    • Ippolito MR, Martis V, Hong C, Wardenaar R, Zerbib J, Spierings DCJ, Ben-David U, Foijer F, Santaguida S. (2021) Aneuploidy-driven genome instability triggers resistance to chemotherapy. Dev Cell.
    • Shoshani O, Bakker B, WangY , Kim DH, Maldonado M, Demarest MA, Artates J, Zhengyu O, Mark A, Wardenaar R, Sasik R, Spierings DCJ, Vitre B, Fisch K, Foijer F, and Cleveland DW.(2021) Transient genomic instability drives tumorigenesis through accelerated clonal evolution. Genes & Development.
    • Jilderda LJ, Zhou L, Foijer F.(2021) Understanding how genetic mutations collaborate with genomic instability in cancer. Cells.  
    • Cohen-Sharir Y, McFarland JM, Abdusamad M, Marquis C, Bernhard SV, Kazachkova M, Tang H, Ippolito MR, Laue K, Zerbib J, Malaby HLH, Jones A, Stautmeister LM, Bockaj I, Wardenaar R, Lyons N, Nagaraja A, Bass AJ, Spierings DCJ, Foijer F, Beroukhim R, Santaguida S, Golub TR, Stumpff J, Storchova Z, and Ben-David U.(2021) Aneuploidy-induced cancer vulnerability to mitotic checkpoint inhibition. Nature.    
    • Schukken KM, Zhu Y, Bakker PL, Koster MH, Harkema L, Youssef SA, de Bruin A, Foijer F.(2021) Acute systemic loss of Mad2 leads to intestinal atrophy in adult mice. Scientific Reports.  
    • Sladky VC, Knapp K, Szabo TG, Braun VZ, Bongiovanni L, van den Bos H, Spierings DC, Westendorp B, Curinha A, Stojakovic T, Scharnagl H, Timelthaler G, Tsuchia K, Pinter M, Semmler G, Foijer F, de Bruin A, Reiberger T, Rohr-Udilova N, Villunger A.(2020) PIDDosome-induced p53-dependent ploidy restriction facilitates hepatocarcinogenesis. EMBO Rep.  
    • Phan TP, Maryniak AL, Boatwright CA, Lee J, Atkins A, Tijhuis A, Spierings DC, Bazzi H, Foijer F, Jordan PW, Stracker TH, Holland AJ.(2020) Centrosome defects cause microcephaly by activating the 53BP1-USP28-TP53 mitotic surveillance pathway. EMBO Journal.    
    • Zhou L, Jilderda LJ, Foijer F.(2020) Exploiting aneuploidy-imposed stresses and coping mechanisms to battle cancer. Open Biology.
    • Saba KH, Cornmark L, Hofvander J, Magnusson L, Nilsson J, van den Bos H, Spierings DC, Foijer F, Staaf J, Brosjö O, Sumathi VP, Lam SW, Szuhai K, Bovée JV, Kovac M, Baumhoer D, Styring E, Nord KH.(2020) Loss of NF2 defines a genetic subgroup of non-FOS-rearranged osteoblastoma. Journal Pathology Clinical Research.
    • Sladky VC, Knapp K, Soratroi C, Heppke J, Eichin F, Rocamora-Reverte L, Szabo TG, Bongiovanni L, Westendorp B, Moreno E, van Liere EA, Bakker B, Spierings DCJ, Wardenaar R, Pereyra D, Starlinger P, Schultze S, Trauner M, Stojakovic T, Scharnagl H, Fava LL, Foijer F, de Bruin A, Villunger A.(2020) E2F-Family Members Engage the PIDDosome to Limit Hepatocyte Ploidy in Liver Development and Regeneration. Developmental Cell.      
    • Andersson N, Bakker B, Karlsson J, Valind A, Holmquist Mengelbier L, Spierings DCJ, Foijer F, Gisselsson D.(2020) Extensive clonal branching shapes the evolutionary history of high-risk pediatric cancers. Cancer Research.  
    • Schukken KM, Lin YC, Bakker PL, Schubert M, Preuss SF, Simon JE, van den Bos H, Storchova Z, Colomé-Tatché M, Bastians H, Spierings DC, Foijer F. (2020) Altering microtubule dynamics is synergistically toxic with spindle assembly checkpoint inhibition. Life Science alliance.
    • Sieben CJ, Jeganathan KB, Nelson GG, Sturmlechner I, Zhang C, van Deursen WH, Bakker B, Foijer F, Li H, Baker DJ, van Deursen JM.(2020) BubR1 allelic effects drive phenotypic heterogeneity in mosaic-variegated aneuploidy progeria syndrome. Journal of Clinical Investigation.  
    • Schubert M, Colomé-Tatché M, Foijer F.(2019) Gene networks in cancer are biased by aneuploidies and sample impurities. Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms.
    • Schoonen PM, Kok YP, Wierenga E, Bakker B, Foijer F, Spierings DCJ, van Vugt MATM.(2019) Premature Mitotic Entry Induced by ATR Inhibition Potentiates Olaparib Inhibition-Mediated Genomic Instability, Inflammatory Signaling, and Cytotoxicity in BRCA2-deficient Cancer Cells. Molecular Oncology.    
    • Hong C, Tijhuis AE, Foijer F.(2019) The cGAS Paradox: Contrasting Roles for cGAS-STING Pathway in Chromosomal Instability. Cells.
    • Bolhaqueiro ACF, Ponsioen B, Bakker B, Spierings DCJ, Klaasen SJ, Papaspyropoulos  A, Dutta D, Hami N, Verlaan-Klink I, van Jaarsveld RH, Lansdorp PM, van de Wetering M, Clevers H, Foijer F, Snippert HJG and Kops GJPL.(2019) Ongoing chromosomal instability and karyotype evolution in human colorectal cancer. Nature Genetics.  
    • Foijer F , Albacker LA, Bakker B, Spierings DC, Yue Y, Xie SZ, Davis S, Lutum-Jehle A, Takemoto D, Hare B, Furey B, Bronson RT, Lansdorp PM, Bradley A, Sorger PK.(2017) Deletion of the MAD2L1 spindle assembly checkpoint gene is tolerated in mouse models of acute T-cell lymphoma and hepatocellular carcinoma. eLIFE.  
    • Bakker B, Taudt A, Belderbos ME, Porubsky D, Spierings DC, de Jong TV, Halsema N, Kazemier HG, Hoekstra-Wakker K, Bradley A, de Bont ES, van den Berg A, Guryev V, Lansdorp PM, Colomé-Tatché M, Foijer F. (2016) Single-cell sequencing reveals karyotype heterogeneity in murine and human malignancies. Genome Biology.
    • van den Bos H, Spierings DC, Taudt AS, Bakker B, Porubský D, Falconer E, Novoa C, Halsema N, Kazemier HG, Hoekstra-Wakker K, Guryev V, den Dunnen WF, Foijer F, Tatché MC, Boddeke HW, Lansdorp PM. (2016) Single-cell whole genome sequencing reveals no evidence for common aneuploidy in normal and Alzheimer’s disease neurons. Genome Biology.
    • Heijink AM, Blomen VA, Bisteau X, Degener F, Matsushita FY, Kaldis P, Foijer F, van Vugt MA. (2015) A haploid genetic screen identifies the G1/S regulatory machinery as a determinant of Wee1 inhibitor sensitivity. PNAS.
    • Simon JE, Bakker B, Foijer F. (2015) CINcere Modelling: What Have Mouse Models for Chromosome Instability Taught Us? Recent Results in Cancer Research.
    • Bakker B, van der Bos H, Lansdorp PM, Foijer F (2015) How to count chromosomes in a cell: An overview of current and novel technologies. Bioessays.
    • Oliveira VL, Foijer F. (2015) Better check late than never: The chromosome segregation checkpoint. Bioessays.
    • Foijer F, Xie SZ, Simon JE, Conte N, Davis S,Kregel E, Jinkers J, Bradley A and Sorger PK,(2014) Chromosome instability induced by Mps1 and p53 mutation generates aggressive lymphomas exhibiting aneuploidy-induced stress. Proceedings of the National Academy of Sciences
    • Foijer F, DiTommaso T, Donati G, Hautaviita K, Xie SZ, Heath E, Smyth I, Watt FM, Sorger PK, Bradley A. (2013) Spindle checkpoint deficiency is tolerated by murine epidermal cells but not hair follicle stem cells. PNAS.
    • Orth JD, Kohler RH, Foijer F, Sorger PK, Weissleder R, Mitchison TJ. (2011) Analysis of mitosis and antimitotic drug responses in tumors by in vivo microscopy and single-cell pharmacodynamics. Cancer research.
    • Foijer F. (2010) CINister thoughts. Biochemical society transactions.
    • van Harn T, Foijer F, van Vugt M, Banerjee R, Yang F, Oostra A, Joenje H, te Riele H. (2010) Loss of Rb proteins causes genomic instability in the absence of mitogenic signaling. Genes & development.
    • Vormer TL, Foijer F, Wielders CL, te Riele H. (2008) Anchorage-independent growth of pocket protein-deficient murine fibroblasts requires bypass of G2 arrest and can be accomplished by expression of TBX2. Molecular and cellular biology.
    • Foijer F, Draviam VM, Sorger PK. (2008) Studying chromosome instability in the mouse. Biochimica Biophysica Acta.
    • Foijer F, Delzenne-Goette E, Dekker M, Te Riele H. (2007) In vivo significance of the G2 restriction point. Cancer research.
    • Foijer F, Simonis M, van Vliet M, Wessels L, Kerkhoven R, Sorger PK, Te Riele H. (2007) Oncogenic pathways impinging on the G2-restriction point. Oncogene.
    • Foijer F, Te Riele H. (2006) Restriction beyond the restriction point: mitogen requirement for G2 passage. Cell division.
    • Foijer F, te Riele H. (2006) Check, double check: the G2 barrier to cancer. Cell cycle.
    • Foijer F, Wolthuis RM, Doodeman V, Medema RH, te Riele H. (2005) Mitogen requirement for cell cycle progression in the absence of pocket protein activity. Cancer cell.
    • Verlinden L, Eelen G, Beullens I, Van Camp M, Van Hummelen P, Engelen K, Van Hellemont R, Marchal K, De Moor B, Foijer F, Te Riele H, Beullens M, Bollen M, Mathieu C, Bouillon R, Verstuyf A. (2005) Characterization of the condensin component Cnap1 and protein kinase Melk as novel E2F target genes down-regulated by 1,25-dihydroxyvitamin D3. The journal of biological chemistry.

  • Klaske Schukken (Postdoc at Cold Spring Harbor Laboratories, per nu)

    Daniel Warmerdam (CRISPR expert at Amsterdam MC, Amsterdam, the Netherlands)

    Stefan Juranek (Group leader, University Clinic Bonn, Germany)

    Judith Simon (Marie-Curie-funded postdoc at Bart’s Cancer Centre, London, UK)

    Weilin Liu (Postdoc at Erasmus MC, Rotterdam, The Netherlands)

    Jorge Garcia-Martinez (Senior Researcher and Data Analyst at Life Length, Madrid, Spain)

    Yinan Zhu (Medical Advisor, Boehringer Ingelheim, Shanghai region, China)

    Bjorn Bakker (Postdoc Crick Institute London)

    Catalina Gaviria (Adjunct professor, University Antioquia, Colombia)

    – Irena Bockaj (UniQure, Amsterdam)

    – Narendra Chunduri (Scientist at Charles Rivers; Leiden)

    – Christy Hong (Postdoc Memorial Sloan Kettering Cancer Center, New York; USA)

    – Jonas Seiler (Scientist at Meatable, Delft)

    – Lin Zhou (Postdoc Boston University)

    – Laura Jilderda (Project manager at PRA, Groningen)

    – Ellie Huizinga (IVF technician at UMCG, Groningen)

    – Michael Schubert (Postdoc at Netherlands Cancer Institute, Amsterdam)

    – Sahil Gupta (CEO Prolevi Bio, Sweden)

    – Amanda Assoni

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