Chromosomal aberrations
Healthy human cells are diploid – they carry each chromosome in two copies. Errors in cell division result in aberrations from this normal chromosome content. Loss or gain of chromosomes strongly affect the physiology of eukaryotic cells and often associate with pathologies, such as in trisomy syndromes (e.g. Down syndrome) or in cancer cells. In our group we use cutting-edge technologies to study the causes and consequences of chromosomal aberrations.

Loss or gain of a single chromosome changes cellular homeostasis
Missegregation of even a single chromosome strongly affects physiology of human cells. Many cells with aberrant chromosome numbers (so called aneuploidy) fail to proliferate. Some can further propagate, but with severe consequences – the protein homeostasis is impaired, the genomic stability is compromised. We created a series of human cell lines that have one chromosome extra (trisomy) or less (monosomy) to study the molecular processes affected by aneuploidy. Using genomics, transcriptomics and proteomics, we analyze genome stability and protein homeostasis in aneuploid cells and how these changes contribute to human pathologies.



Impact of chromosome gain on DNA replication
Presence of extra chromosomes impairs proliferation of aneuploid cells and affects expression of DNA replication factors. These cells show several hallmarks of replication stress and accumulate DNA damage and additional chromosomal aberration. We elucidate the mechanisms that contribute to replication stress in aneuploid cells.

Consequences of chromosome loss
Loss of a single chromosome – monosomy – has severe consequences in human cells and is not compatible with survival. We have established a model system to elucidate what molecular mechanisms underlie the severe consequences of monosomy.

Maintenance of protein homeostasis in response to chromosomal imbalance
Comparision of genome, transciptome and proteome determined that genes from the extra chromosomes are normally transcribed and translated, but that expression levels of many proteins are adjusted to wild type levels. We study how autophagy, proteasomal degradation affect protein homeostasis in aneuploid cells on a global scale. Moreover, we elaborate the mechanism of autophagy activation in response to aneuploidy.

Whole genome doubling contributes to genome evolution
Failure of cytokinesis generates binucleated cells with a doubled genome content – a tetraploid cell. While most tetraploid cells cannot further proliferate, some cells survive with increased chromosomal instability (CIN) and extensive aneuploidy. Sequencing of cancer genomes suggests that about 40 % of all cancers have undergone whole-genome doubling at some point during tumorigenesis. We study molecular mechanisms that contribute to changes in tetraploid cells and how they contribute to tumor formation.


Want to find out more about Aneuploidy?

Check out the book “Aneuploidy in health and disease”