Lens Group

Susanne LensLens group: How to maintain a stable genome?

 

Group leader: Susanne Lens (about group leader)

Research topics

Cancer arises as a consequence of uncontrolled cell division. In healthy tissues, cell division is a well-controlled process during which both our duplicated genetic and cytoplasmic material is equally distributed over the two newly formed daughter cells, such that after a round of cell division each daughter cell has a complete set of 46 chromosomes. In marked contrast to normal cells, many human cancer cells have gained or lost whole chromosomes, i.e. these cells display numerical chromosomal instability and as a consequence have an aneuploid genome. Whether CIN is cause or consequence of cancer has for long been a matter of debate, but evidence is accumulating that it can indeed support tumorigenesis in certain tissues by promoting, for instance, the loss of heterozygosity of certain tumorsuppressor genes. My lab studies how chromosomal stability is normally ensured and aims to identify factors that control the chromosome segregation process.

Chromosomal instability is a process of errors that take place during cell division. Failure to properly connect the duplicated sister-chromatids to the microtubules of the mitotic spindle, a dysfunctional mitotic checkpoint that fails to respond to these mis-attachments or the inability to complete cytoplasmic division (cytokinesis), can all result in chromosome segregation errors and eventually in aneuploidy.

A group of proteins termed the "chromosomal passenger complex" (CPC) regulates all these processes in the dividing cell; it detaches faulty chromosome-microtubule interactions that when left uncorrected would result in segregation errors, it is essential for a robust mitotic checkpoint and it controls cytokinesis. The CPC consists of at least four interacting proteins: Aurora B, INCENP, survivin and borealin. While Aurora B is the enzymatic core of the complex, the other subunits control its enzymatic activity and guide the enzyme to its specific locations in mitotic cell.

The overall aim of my research is to unravel how the chromosomal passenger complex ensures chromosomal stability and to investigate if its deregulation can be a cause of aneuploidy in tumor cells.