Research Groups

Genomic Instability in Development and Disease

Aneuploidy, an abnormal number of chromosomes, is a key feature of cancer cells and is furthermore associated with aging-related pathologies such as Alzheimer’s disease.
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  • Info
  • Publications
  • 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
    Weilin Liu
    PhD Students
    Laura J. Jilderda
    Klaske Schukken
    Judith Simon
    Technicians
  • In our lab, we are interested in how aneuploidy arises and even more importantly, in the consequences of aneuploidy for cells, tissues and whole organisms. To this aim, we have developed state of the art murine models in which we can provoke aneuploidy in tissues of choice. These models are revealing that aneuploidy itself can be a potent driver of malignant transformation, for instance in T-cells, provoking highly aggressive lymphomas that resemble certain paediatric malignancies. In other tissues, for instance in skin, aneuploidy appears to provoke more of an accelerated aging phenotype, emphasizing the dual role that aneuploidy plays in cell biology. We are trying to decipher the mechanism of these -almost paradoxical - responses in our existing models, but we are also actively developing new models. One example is a model to visualize aneuploidy in the skin of living animals using high resolution intravital imaging, allowing us to monitor the response to aneuploidy at the single cell level in the context of an unperturbed tissue. A better understanding of the molecular consequences of aneuploidy will inevitably lead to novel therapies targeting this hallmark of tumour cells. Furthermore, the number of aneuploid cells in an organism also appears to increase with age. Our models therefore also provide a unique resource to study the relation between aneuploidy, cancer and aging.
    • 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, Bakker PL, Conte N, Davis S, Kregel E, Jonkers J, Bradley A, Sorger PK. (2014) Chromosome instability induced by Mps1 and p53 mutation generates aggressive lymphomas exhibiting aneuploidy-induced stress. PNAS.
    • 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.
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