René Bernards Group

René Bernards

Oncode Investigator at NKI

My research

René Bernards studied adenovirus transformation for his PhD research with Alex van der Eb in Leiden. He joined the laboratory of Robert Weinberg at the Whitehead Institute in Cambridge, USA for his postdoctoral training. He was appointed assistant professor at the Massachusetts General Hospital Cancer Center in 1988. In 1992 he joined the Netherlands Cancer Institute in Amsterdam. In 1994 he was also appointed part time professor of molecular carcinogenesis at Utrecht University, The Netherlands.

During his PhD research, he showed that the difference between oncogenic and non-oncogenic adenoviruses was primarily due to their differential ability to switch off the expression of MHC class I antigens, allowing evasion of T cell immune responses. During his postdoctoral work, he showed that downregulation of MHC class I antigens is also a property of the MYCN oncoprotein and, in collaboration with Stephen Friend, isolated the first tumor suppressor gene, RB1.

After returning to Amsterdam in 1992, his major scientific accomplishments include the development of MammaPrint, the first molecular diagnostic test for personalized treatment of breast cancer that has been used clinically since 2004 to select patients for adjuvant therapy. Recently, MammaPrint was validated in a large phase III clinical study, which demonstrated that over 100,000 women in the EU and US that are treated with chemotherapy annually can safely forego this toxic treatment without loss of survival benefit.

His laboratory also developed the first shRNA vector for gene silencing in mammalian cells and used this vector to create the first genome-scale library of shRNA vectors, enabling genome-wide loss of function genetic screens in mammalian cells. His laboratory has used this vector collection to identify the PI3K pathway as a major determinant of resistance to herceptin in breast cancer and to identify the CYLD tumor suppressor gene as a regulator of NF-kB signaling, which suggested a strategy to treat cylindromatosis. His laboratory also used genetic screens to identify a number of particularly powerful drug combinations for the treatment of cancer, based on the concept of synthetic lethality. This work identified the combination of a BRAF inhibitor and an EGFR inhibitor as effective for the treatment of BRAF mutant colon cancer. There are currently five clinical trials ongoing that test the efficacy of the combination therapies suggested by genetic screens from his laboratory.

He has co-founded four companies: Prolifix (developed belinostat for treatment of peripheral T cell lymphoma), Agendia (developed MammaPrint for breast cancer diagnosis), Qameleon Therapeutics (Qamelostat for treatment of BRAF inhibitor-resistant melanoma) and Oncosence (pro senescence therapy for cancer).

Awards

  • 2013: Academy Professor Prize, Royal Netherlands Academy of Arts and Sciences.
  • 2012: Queen Wilhelmina Research Prize, Dutch Cancer Society. 
  • 2011: Scrip Best Partnership Alliance Award for colorectal cancer collaboration with AstraZeneca and Agendia. 
  • 2009: Fellow, European Academy of Cancer Sciences. 
  • 2007: ESMO Lifetime Achievement Award in Translational Research in Breast Cancer. 
  • 2007: Member, Royal Netherlands Academy of Arts and Sciences
  • 2005: Ernst W. Bertner Award for Cancer Research, M.D. Anderson Cancer Center. 
  • 2005: Spinoza award, Netherlands Organization for Scientific Research.
  • 2005: Member, Academia Europea. 
  • 2005: Pezcoller Foundation-FECS Recognition for Contribution to Oncology. 
  • 2004: Josephine Nefkens award, Erasmus University, Rotterdam. 
  • 1992: Pionier Award, Netherlands Organization for Scientific Research.
  • 1989: Searle Scholarship award. 
  • 1988: Edward Mallinckrodt Foundation award. 
  • 1985: Constantijn and Christiaan Huygens Fellowship, Netherlands Organization for Scientific Research.


Key publications

  1. Berns, K., Hijmans, E. M., Mullenders, J., Brummelkamp, T. R., Velds, A., Heimerikx, M., ... & Bernards, R. (2004). A large-scale RNAi screen in human cells identifies new components of the p53 pathway. Nature428(6981), 431.
  2. Huang, S., Hölzel, M., Knijnenburg, T., Schlicker, A., Roepman, P., McDermott, U., ... & Bernards, R. (2012). MED12 controls the response to multiple targeted cancer drugs through direct regulation of TGFβ receptor signaling. Cell, 151, 937-950.
  3. Prahallad, A., Sun, C., Huang, S., Di Nicolantonio, F., Salazar, R., Zecchin, D., ... & Bernards, R. (2012). Unresponsiveness of colon cancer to BRAF (V600E) inhibition through feedback activation of EGFR. Nature483(7388), 100.

  4. Sun, C., Wang, L., Huang, S., Heynen, G. J., Prahallad, A., Robert, C., ... & Bernards, R. (2014). Reversible and adaptive resistance to BRAF (V600E) inhibition in melanoma. Nature508(7494), 118.

  5. Van De Vijver, M. J., He, Y. D., Van't Veer, L. J., Dai, H., Hart, A. A., Voskuil, D. W., ... & Bernards, R. (2002). A gene-expression signature as a predictor of survival in breast cancer. New England Journal of Medicine347(25), 1999-2009.

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René Bernards Oncode Investigator

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