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Division Signaling and Functional Genomics


 

 

 

Research Overview

 

We are interested in cellular signaling transduction and its role in cell homeostasis, differentiation and disease. During development and homeostasis, cells constantly receive signals that determine whether they divide, differentiate or die. Inappropriate control of signaling has been linked with many diseases and is frequently associated with cancer. We study principal mechanism of signal transduction by genomic and cell biological responses.

 

Systematic analysis of Wnt signaling pathways in development and cancer

IWnt pathways are an evolutionarily conserved signal transduction cassette that play key during development. Aberrant activation of the Wnt signaling pathway has been linked tothe development of colorectal cancer. Mutations that inactivate the APC tumour suppressor or activate beta-catenin are found in 90% of all human colorectal cancers. Similar Wnt activating mutations are also found in hepatocarcinomas and many other tumors.

We are interested in the identification of novel Wnt pathway components and to understand how Wnt signaling is regulated in development and disease. A particular focus of our studies are on specific secretory pathways for Wnt ligands.

 

Synthetic genetic interaction networks

Reverse genetics in cells amenable for high-throughput analysis to rapidly investigate synthetic genetic interactions. Synthetic genetic interactions are defined as phenotypes caused by two perturbations which are not apparent in either single perturbation. For example, such phenotypes could be caused by genes that act in a redundant manner, or a gene that only shows a phenotype under the influence of an exogenous perturbation, such as a drug treatment. Genetic interactions have been used to identify components that are otherwise masked due to multigenic traits, complex phenotypes or early lethality in metazoans. Also, synthetic lethals can lead to the identification of genes that can act in concert with small molecules to enhance, or suppress the cytotoxity of cancer therapeutics. We use synthetic genetic analysis and large-scale phenotyping in model organisms and human cells to delineate interaction of pathways and other environmental perturbations.

 

High-throughput biology and technology development

We develop technologies for high-throughput screening in cultured cells and bioinformatic methods to analyze large phenotypic data sets, including the development of miniaturized assay formats, new approaches for massively parallel perturbation analysis and phenotyping by deep-sequencing.