Leiden / Amsterdam Center for Drug Research – Leiden University, The Netherlands
We perform RNAi screens largely dedicated to cellular signaling in the areas of cancer and drug safety.
A first major research theme is the integration of functional genomics with gene expression and posttranslational modification datasets to unravel cellular responses to genotoxic and non-genotoxic carcinogens at a systems level; to better understand adverse drug reactions; and to identify drug targets involved in chemoresistance.
In a second theme, we use RNAi screening to identify candidate regulators of NFkB nuclear translocation. Real time automated confocal imaging coupled to bioinformatics is used to follow NFkB oscillation in the context of cytokine stress response signaling. Candidate genes are likely regulators of immune-mediated adverse effect responses in drug toxicity.
In a second research theme, we have built a pipeline of in vitro and in vivo assays aimed at understanding signaling pathways that regulate adhesion and migration. Using automated real time microscopy and quantitative multi parameter image analysis algorithms; we identify new regulators of cell adhesion/migration dynamics. Such hits are validated using 3D in vitro assays; zebrafish xenografts; and mouse orthotopic transplantation models to identify important players in cancer metastasis.
For more information, visit our website at toxicol.lacdr.gorlaeus.net
Primary Contacts:
Erik HJ Danen
Email
Bob van de Water
Email