The Netherlands Cancer Insitute - Antoni van Leeuwenhoek Hospital

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The Netherlands Cancer Insitute - Antoni van Leeuwenhoek Hospital

	René Bernards Roderick Beijersbergen

	René Bernards and Roderick Beijersbergen are in the division of Molecular Carcinogenesis at the Netherlands Cancer Institute. Their laboratories focus on the development and application of innovative tools to perform genome-wide functional screens in mammalian cells for the identification of genes that act in cancer relevant pathways. With the use of high throughput gain-of-function genetic screens with retroviral cDNA libraries and loss-of-function screens with RNA interference libraries, novel components of important signaling pathways will be identified that could represent novel drug targets. In addition, these functional approaches are used to understand the mechanism of action of anti cancer drugs. Over the last years, Drs Bernards and Beijersbergen have generated large collections of shRNA vectors that are used to perform large scale screens for loss of function phenotypes in several central cancer pathways, including the p53, TGFß, NFkB and AKT pathways. They also address the problem of unresponsiveness to therapy by using functional genomic approaches to identify genes that contribute to drug resistance in cancer cells. With the development of tools to perform loss-of function screens, technologies have become available that facilitate the discovery of synthetic lethal interactions in mammalian cells. Our goal is to identify and understand synthetic lethal interactions involving genes frequently found mutated in human cancer. The identification of synthetic lethal interaction with tumor specific genetic alterations can ultimately lead to the generation of "genotype-specific" drugs. The research projects are facilitated by the NKI robotics and screening center that has a fully integrated platform for running automated cell based assays. The facility is equipped to maintain and use large collections of genomic tools such shRNA libraries, siRNA collections and cDNA collections. For more information visit www.screeninc.nl or Rene Bernards homepage Contact Details The Netherlands Cancer Institute Division of Molecular Carcinogenesis Plesmanlaan 121, 1066 CX, Amsterdam The Netherlands Phone: 31 20 512 1960/1952 Fax: 31 20 512 1954

	Recent Publications Nijman SM, Luna-Vargas MP, Velds A, Brummelkamp TR, Dirac AM, Sixma TK, Bernards R. A genomic and functional inventory of deubiquitinating enzymes. Cell. 2005 Dec 2;123(5):773-86. Dirac AM, Nijman SM, Brummelkamp TR, Bernards R. Functional annotation of deubiquitinating enzymes using RNA interference. Methods Enzymol. 2005;398:554-67. Rowland BD, Bernards R, Peeper DS. The KLF4 tumour suppressor is a transcriptional repressor of p53 that acts as a context-dependent oncogene. Nat Cell Biol. 2005 Oct 23. Epping MT, Wang L, Edel MJ, Carlee L, Hernandez M, Bernards R. The human tumor antigen PRAME is a dominant repressor of retinoic acid receptor signaling. Cell. 2005 Sep 23;122(6):835-47. Brummelkamp TR, Berns K, Hijmans EM, Mullenders J, Fabius A, Heimerikx M, Velds A, Kerkhoven RM, Madiredjo M, Bernards R, Beijersbergen RL. Functional identification of cancer-relevant genes through large-scale RNA interference screens in mammalian cells. Cold Spring Harb Symp Quant Biol. 2004;69:439-45. Kolfschoten IG, van Leeuwen B, Berns K, Mullenders J, Beijersbergen RL, Bernards R, Voorhoeve PM, Agami R. A genetic screen identifies PITX1 as a suppressor of RAS activity and tumorigenicity. Cell. 2005 Jun 17;121(6):849-58. Bernards R. A functional approach to questions about life, death, and phosphorylation. Cancer Cell. 2005 Jun;7(6):503-4. Nijman SM, Huang TT, Dirac AM, Brummelkamp TR, Kerkhoven RM, D'Andrea AD, Bernards R. The deubiquitinating enzyme USP1 regulates the Fanconi anemia pathway. Mol Cell. 2005 Feb 4;17(3):331-9. Bernards R. Wip-ing out cancer.Nat Genet. 2004 Apr;36(4):319-20. Berns K, Hijmans EM, Mullenders J, Brummelkamp TR, Velds A, Heimerikx M, Kerkhoven RM, Madiredjo M, Nijkamp W, Weigelt B, Agami R, Ge W, Cavet G, Linsley PS, Beijersbergen RL, Bernards R. A large-scale RNAi screen in human cells identifies new components of the p53 pathway. Nature. 2004 Mar 25;428(6981):431-7. Das AT, Brummelkamp TR, Westerhout EM, Vink M, Madiredjo M, Bernards R, Berkhout B. Human immunodeficiency virus type 1 escapes from RNA interference-mediated inhibition. J Virol. 2004 Mar;78(5):2601-5. Brummelkamp TR, Bernards R. New tools for functional mammalian cancer genetics. Nat Rev Cancer. 2003 Oct;3(10):781-9. Review. Back to Netherlands Cancer Institute