Mechanisms of cell death
Cells can get damaged by many factors, for instance sunlight, aging or drugs. Usually cells are able to repair themselves but sometimes the damage is too severe and the cell dies. Tumor cells on the other hand, are damaged cells that do not die and proliferate at every cost. We investigate how cells get damaged and repair and how we can use mechanisms of cell death to fight tumor cells.
Image: Change associated with programmed cell death: The morphology of nuclear DNA (blue) 1h (top) and 24 h (bottom) after injecting an apoptosis inducing agent in a tumor cell.
From: Zhang et al. 2003
Topics within this research theme
Failure to recognize and respond to DNA damage is associated with premature aging disorders and cancer. We use microarray analysis and (phospho)proteomics to characterize the signal transduction networks that are triggered by DNA damage. In addition, we perform large-scale siRNA screens to identify proteins that are involved in the response to DNA damaging chemotherapeutic compounds.
Although medication is meant to cure diseases, drugs may cause harm to the body even at normal doses. Especially the liver and kidneys are susceptible to adverse drug reactions. We study the mechanisms of toxicity and repair in these organs, using transgenic mouse models, three dimensional in vitro organoid culture, transcriptomics and functional genomics.
Tumor cells are often considered to be fast growing super cells, but we see them as cells with many weaknesses. For although cancer cells have lost the property to die efficiently, proteins like apoptin can restore this feature and lead to tumor-specific cell death. We want to understand more about the fundamental processes in which apoptin is involved.
In tumors of the nervous system like neuroblastoma, the protein DCL plays an important role. If the DCL-gene is suppressed, the cells stop dividing. We want to know if we can suppress the gene using RNAi and whether therapeutic use of this method is possible.