Research Theme 2

Understanding the critical drivers of tumour growth and the causes of resistance.

Background

Both genetic and epigenetic alterations are at the basis of tumour development and the acquisition of resistance to treatment. The epigenetic makeup of the “cell of origin” may also strongly influence tumour development. The challenge is to identify these critical genetic and epigenetic alterations and to understand the underlying biology in order to design more effective interventions.

Theme aims

  1. Uncovering drivers and causes of resistance – Using genome-wide genetic screens that employ CRISPR/Cas9 technology in well-established model systems, we aim to identify driver genes of tumour growth and drug resistance. We will focus on epigenetic alterations and their underlying mechanisms, as these are, in theory, reversible.
  2. Studying driver defects in tumour samples – Using state-of-the-art sequencing technologies we will create longitudinal catalogues of genetic variants in well-defined tumour samples. This will allow the identification of driver and passenger mutations and whether these were acquired during treatment.
  3. Developing bioinformatics tools – Improved omics technologies require further advances in integrated analysis methods. Integrated analyses of shared worldwide data sets with newly developed tools may result in the identification of new therapeutic targets.
  4. Validating of new drivers – Drivers we have identified in aims 1-3 will be validated using CRISPR/Cas9 gain- or loss-of-function experiments in vitro. Preclinical mouse models will be generated to study tumour formation and treatment in vivo.

Please find a more detailed description in our Strategic Plan.

Theme leader

Jan Paul Medema Research Management Committee

Co-leader

Lodewyk Wessels Oncode Investigator
Ruud Delwel Oncode Investigator

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