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.
Group Leader of the Laboratory of Genomic Instability in Development and Disease
Mouse models for aneuploidy, spindle checkpoint, chromosomal instability, CIN, aneuploidy and cancer, aneuploidy and ageing
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.
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)