Patrick Meraldi

Human Cell Division in normal and cancer cells

 Our group investigates the fundamental mechanisms of cell division ensuring faithful chromosome segregation in human cells, how a deregulation of these mechanisms contribute to genetic instability in cancer cells, and how this erroneous process can reveal new targets for anti-cancer treatments or be exploited by novel anti-cancer drugs. The goal of cell division is to separate the duplicated sister chromatids (in figure above in red) with the help of the mitotic spindle (in green). We aim to obtain an integrated view of chromosome segregation that considers all the elements of the mitotic machinery, including centrosomes, the different microtubule populations of the mitotic spindle, kinetochores, chromosomes, and the cell cortex. Our major focus is to understand how these different activities and entities are coordinated in space and time to ensure a faithful and accurate cell division.

Moreover, we aim to understand how defects in these processes lead to chromosome segregation errors and contribute to human pathologies, such as primary microcephaly and cancer. Indeed, 85% of solid human cancer tissues are aneuploid and have an elevated tendency to loose or gain chromosomes. Chromosomal instability and aneuploidy are not only symptoms of cancer cells, they can directly cause or enhance cancer formation, as they create dosage imbalances between oncogenes and tumour suppressors, and contribute to the development of cancer drug resistances.

Our studies rely on high-resolution quantitative light microscopy and extensive image analysis; combined with chemical and genetic perturbations, cell biology, and biochemistry.

Our group is part of the Translational Research Centre in Oncohematology