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Molecular Carcinogenesis: Roderick Beijersbergen

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Roderick Beijersbergen Ph.D.Group leader, Head of High Content Screening Facility

About Roderick Beijersbergen

Signaling Networks in Cancer

This research group is using functional genomic technologies for the identification of novel targets for the development of anticancer drugs. We are developing our screening systems along three lines:

  1. the identification of novel players in important cellular pathways deregulated in cancer,
  2. the elucidation of the mechanism of drug action and resistance and 
  3. the identification of (synthetic or synergistic) lethal interactions to identify genotype specific drug targets.

Over the last years my group has invested in the generation of tools to perform functional genetic screens with special emphasis on loss-of-function cell based screens. To facilitate loss of function genetic screens we have developed large collections of shRNA knockdown vectors, targeting large numbers of both human and mouse genes. The development of these technologies has opened up the possibility to perform large scale mammalian somatic genetics.

Apart from the construction of large collections of shRNA vectors, my lab has a strong focus on the development of novel technologies using RNAi for gene identification. One of these technologies, shRNA bar code screening, although still under development, has already demonstrated its power in numerous biological screening systems. We have further extended our technology platform with siRNA and esiRNA technologies and will apply these technologies to identify novel components of important cellular networks that are affected or deregulated in human cancer. The goal of these projects is to identify novel drug targets beyond the classical oncogenes and tumor suppressor genes with particular emphasis on those targets that can be used in a tumor specific window. Examples of the use of these technologies are the identification of five novel genes that act in the p53 pathway and upon activation result in a bypass of a p53 mediated cell cycle arrest and the finding that intrinsic DNA damage signalling, characteristic for tumor cells, mediates the outcome of a novel type of drugs based on their capacity to re-activate the p53 pathway.

At this moment a considerable part of our efforts is aimed at the development and implementation of biological screens based on (multiple) complex phenotypes. An integral part of this effort is the realization of an automated high content screening platform with state-of-the-art image analysis software, database development and statistical analysis, integrated with bioinformatics. We believe that the combination of loss-of-function technologies with the ability to explore more complex phenotypes on a single cell level will significantly enhance the identification of novel targets and further insights in the molecular mechanisms leading to cancer.

Co-workers

Lorenzo Bombardelli

Lorenzo Bombardelli

Postdoctoral Fellow

Experience

I'm a researcher with extensive experience in oncology and biotechnology. Since my Ph.D (State University of New York at Stonybrook, 2008) I worked on cancer genetics, preclinical target validation and experimental therapies.

My current research focuses on understanding drug toxicity and developing methods to prevent it. Failures in late clinical trials are a burden for patients and companies and often undetectable in preclinical studies. My goal is to develop a high-throughput technology to precisely and quantitatively detect activations of liver toxicity-triggering pathways. Combining such technology with genetic screens will lead to the discovery of mechanisms to modulate and prevent toxicity.

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Cor Lieftink

Bioinformatician

Experience

My professional background is 20+ years in building computer systems, especially databases. I have extensive experience with the programming tools Java and R.

At the NKI Robotics and Screening Center my main task is to support the storage and analysis of experimental data.  Data generated by the different high throughput screening platforms including siRNA, pooled shRNA and compound screens. For each platform  a pipeline has been created for processing and analysis that run on our server system.

I also participate in the Cancer Systems Biology Center, which aims to develop predictive models for therapy response.

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Ben Morris

Technician

Experience

As a member of the Screening and Robotics facility, I am actively involved in setting up diverse cancer related compound and RNAi based screens utilizing our in house libraries.  The role involves communicating and advising researchers on the optimization and set up of their screens, preparing library plates for screening and training researchers on our HTS equipment. 

My work also includes the programming, maintenance and validation of our high throughput liquid handlers and readers. 

 

 

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Wouter Nijkamp

Lab Manager

Experience

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Key publications View All Publications

  • MED12 controls the response to multiple cancer drugs through regulation of TGF-β receptor signaling.

    Cell. 2012; 151: 937-50

    Huang S, Hölzel M, Knijnenburg T, Schlicker A, Roepman P, McDermott U, Garnett M, Grernrum W, Sun C, Prahallad A, Groenendijk FH, Mittempergher L, Nijkamp W, Neefjes J, Salazar R, Ten Dijke P, Uramoto H, Tanaka F, Beijersbergen RL, Wessels LF, Bernards R.

     

    link to PubMed
  • Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR

    Nature. 2012; 483: 100-3

    Prahallad A, Sun C, Huang S, Di Nicolantonio F, Salazar R, Zecchin D, Beijersbergen RL, Bardelli A, Bernards R.

     

    link to PubMed
 
 

Recent publications View All Publications

  • J Exp Med. 2018 Dec 3;215(12):3115-3135

    J Exp Med. 2018 Dec 3;215(12):3115-3135

    Serresi M, Siteur B, Hulsman D, Company C, Schmitt MJ, Lieftink C, Morris B, Cesaroni M, Proost N, Beijersbergen RL, van Lohuizen M, Gargiulo G

    link to PubMed
  • A role for the unfolded protein response stress sensor ERN1 in regulating the response to MEK inhibitors in KRAS mutant colon cancers

    Genome Med. 2018 Nov 27;10(1):90

    Šuštić T, van Wageningen S, Bosdriesz E, Reid RJD, Dittmar J, Lieftink C, Beijersbergen RL, Wessels LFA, Rothstein R, Bernards R

    link to PubMed
 

Contact

  • Office manager

    Patty Lagerweij

  • E-mail

    p.lagerweij@nki.nl

  • Telephone Number

    +31 20 512 6973

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