Genomic Instability in Development and Disease

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.