Chromosomal instability, aneuploidy and cancer
Cell division, inner centromere, aneuploidy
Research aim
Understanding the molecular mechanisms that ensure error-free propagation of the genome during cell division and revealing the causes and consequences of chromosomal instability and aneuploidy in cancer.
About us
Most solid tumors display an abnormal number of chromosomes, known as aneuploidy. Aneuploidy is a frequent consequence of chromosomal instability (CIN), the erroneous segregation of the duplicated chromosomes during cell division. CIN and aneuploidy correlate with tumor heterogeneity, drug resistance, and poor patient prognosis. Our research aims to decipher the molecular principles that ensure error-free chromosome segregation during cell division, and to understand how different (cancer) tissue types can cope with the gains or losses of specific chromosomes. With our fundamental research, we strive to gain mechanistic insights into cancer-driving events and to identify targets for potential novel anti-cancer therapies. Specific research topics are:
The inner centromere network. The inner centromere is a specialized chromosome structure on which protein activities accumulate that control sister-chromatid cohesion and chromosome-microtubule connections. We investigate inner centromere protein network regulation, and how network perturbations induce CIN.
Cancer-specific aneuploidy signatures. Different cancer types exhibit characteristic subsets of whole or partial chromosomal gains and losses. We develop chromosome manipulation approaches in living human cells to induce or revert chromosome-specific aneuploidies. Using these innovative methods we aim to identify drivers of tissue-specific aneuploidies and to unravel their contribution to cancer progression and maintenance.