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Molecular Carcinogenesis: René Bernards

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René Bernards, Ph.D. professorGroup leader

About René Bernards

Functional Cancer Genetics

Cancer remains difficult to treat, even with the new generation of targeted cancer drugs. By far the most formidable obstacle is the rapid emergence of therapy resistance. Indeed, many of the new cancer drugs elicit powerful initial responses, leading to dramatic effects on progression free survival, but far less long-term benefit is seen in terms of overall survival.

Combination therapies can help fight therapy resistance, but with an arsenal of over 1000 cancer drugs in clinical development, the number of possible combinations seems nearly endless. In my laboratory we employ functional genetic screens to find powerful combinations of cancer drugs by exploiting the concept of "synthetic lethality". Using RNA interference-based genetic screens with collections of shRNAs that target drugable gene families, we search for genes whose inactivation is particularly synergistic with clinically-relevant cancer drugs. Such screens can identify drug combinations that are far more powerful than the sum of the two single agents. We aim to understand the molecular rationale for the observed synergy between two cancer drugs. Once we have insight into the molecular mechanism, we aim to bring such rationally-designed combinations to the cancer clinic as soon as possible through collaboration with clinicians in our comprehensive cancer center (See for instance NCT01719380).

A second and more recent line of research concerns the identification of actionable genome alterations in cancer through next generation sequencing. We have developed a kinome-centered DNA and RNA sequencing platform to specifically identify clinically-relevant alterations in kinase genes in human cancer. This effort is closely linked to our joint effort within the Dutch Center for Personalized Cancer Treatment (www.cpct.nl/en.aspx), of which Bernards is one of the founding members. 

Link to e-cancer interview June 2014

Co-workers

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Katrien Berns

Associate Staff scientist

Experience

I started as an undergraduate student in Rene Bernards lab in 1995 and have continued working in his group as a PhD student, postdoc and currently as a staff scientist. My main focus has been to develop and perform functional genetic screens to gain more insight into mechanisms of action of oncogenes and tumor suppressor genes.

Furthermore, I use functional genomic approaches to identify mechanisms of primary and acquired drug resistance.  The ultimate goal of all these studies is to translate novel findings into more optimal anti-cancer treatment strategies. I find it very motivating to contribute to this important goal.

 

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Astrid Bosma

Technician

Experience

For the last 18 years I've been working as a technician at the NKI. The first 13 years with Laura van 't Veer on the subject of CTC (Circulating Tumor Cells).

At this moment I'm working in the group of Rene Bernards; by kinome capture we try to discover new signaling pathways who contribute to cancer. In addition we do RNA sequencing.

 

 

 

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Diede Brunen

Ph.D. student

Experience

I studied Biomedical Sciences at Utrecht University and obtained a Master's degree in Infection and Immunology. During my Master, I performed internships at the department of Molecular Immunology at the Wilhelmina Kinderziekenhuis (Utrecht) and in the Cell Biology Department of the Sick Kids Hospital in Toronto, Canada.

I joined the lab of Prof. Dr. Rene Bernards at the end of 2012 as a PhD student. Here, I study the role of epithelial-to-mesenchymal transition (EMT) in cancer. Furthermore, using RNA interference genetic screens, I aim to identify genes that modulate the response to cancer drugs.

 

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Begona Diosdado

Pathologist, PhD

Experience

I am a pathologist interested in molecular biology of cancer and bringing basic science findings into clinical applications.

At present I am a Dutch Cancer Society Fellow interested in understanding the molecular pathogenesis of the described colorectal cancer molecular subtypes and the translation of these findings into targeted therapies. To translate the colorectal cancer genetic pathway additions into novel combination targeted therapies I will be making use of functional genetic screens and colorectal cancer 3D organoid models.

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Annemieke Gennissen

Technician

Experience

 

 

 

 

 

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Marielle Hijmans

Technician

Experience

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Horlings, Hugo

Hugo Horlings

Postdoctoral Fellow

Experience

I have been awarded by a translational and applied cancer research fellowship from the Dutch Cancer Society (KWF). During this fellowship (4 years) I want to focus on identification of the genetic make-up of the tumor contributing to therapy resistance and poor prognosis of patients with breast and ovarian cancer.

The projects described in this proposal will give me opportunities to obtain extensive skills in the application of large- scale and high-throughput genomics technologies in clinical settings, which will be essential for a pathologist to make "precision" medicine a reality.

The fellowship will be in collaboration with the department of pathology of the AvL, Prof. Rene Bernards, Prof. David Huntsman, Prof. Marc van de Vijver and Prof. Howard Chang.

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Rodrigo Leite de Oliveira

Postdoctoral Fellow

Experience

I am a Portuguese pharmacist with a PhD in Biomedicine by the University of Leuven (Belgium). During my doctoral studies, I gained expertize in the field of oxygen sensors with particular focus on tumor angiogenesis and metastasis. 

As a postdoctoral fellow at the NKI, I am investigating strategies to improve the efficiency of antiangiogenic therapies in breast cancer.

 

 

 

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Mainardi, Sara

Sara Mainardi

Postdoctoral Fellow

Experience

I studied Biotechnology at the University of Rome La Sapienza (Italy)
and I carried out my PhD studies at The Spanish National Cancer Institute
(CNIO) in Madrid (Spain) under the supervision of Dr. Mariano Barbacid. There I
studied the cell of origin of non small cell lung cancer using genetically
engineered mouse models.

I joined the group of Dr. Rene Bernards at the NKI in
December 2013 as a postdoctoral fellow to cultivate my interests in
translational research. My work will be mainly focused on the use of 3D
organoid cultures for the discovery of genetic dependencies in colorectal
cancer. 

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Mulero Sanchez, Antonio

Antonio Mulero Sanchez

Technician

Experience

In September 2016 I obtained my MSc degree in Translational Biomedicine at the university of Barcelona (Spain), during the master thesis I moved to Amsterdam to do the internship in the Netherlands Cancer Institute (NKI).

Currently, I am continuing the project I started during my master's in the group of professor René Benards as a Technician. The project I am developing is based on the role of PTPN11/SHP2 in different K-Ras mutant cancers.  K-ras is commonly mutated in different cancers as colon, lung and pancreas. In order to find out a new and better treatment, we are working to see if there is synthetic lethal interaction between MEK inhibitor and a novel small molecule targeting SHP2 protein.

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Neto, Joao

Joao Neto

PhD student

Experience

I studied Biochemistry at University of Aveiro, in Portugal, and obtained a Master's degree in Biotechnology in July 2015.

I joined the lab of Prof. Rene Bernards in September 2015 as a PhD student.  Here, I am studying population dynamics by following single-cells fate using barcoding technology. With this approach we aim to aim modulate the response of cell populations to anti-cancer drugs, so as to develop better therapeutic approaches.

 

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Pogacar, Ziva

Pogačar, Živa

Ph.D. student

Experience

I obtained my Bachelor's degree in Biotechnology from University of Ljubljana, Slovenia. I continued with the Master's program Molecular and functional biology and graduated in September 2015 from University of Ljubljana.

 

I joined the group of prof. Bernards in October 2015, to work on resistance mechanism to EGFR inhibitors in colon cancer. By performing genome-wide screens using CRISPR technology we aim to identify novel resistance mechanisms that could lead to new combination treatment.

 

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Sustic, Tonci

Tonći Šuštić

Ph.D. Student

Experience

I graduated from the Molecular Biology program at the University of Zagreb, having completed diploma thesis research on the role of HoxB13 in genetically defined ovarian cancer cell lines.

I next obtained a Master's degree in Medical Science (Oncology) from the University of Cambridge analysing metabolomic changes in oncogene-induced senescence. I spent the following year working as a Research Assistant at the Cambridge Institute for Medical Research where I gained experience in derivation of haematopoietic progenitor cells and learned the basics of multicolor flow cytometry.

I joined the Bernards lab in September 2013 to focus on targeted therapies for lung cancer.

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Liqin Wang

Ph.D. student

Experience

For many cancer cases, mono-targeted drug therapy can work in the short term, but cancer often develops resistance mechanisms to escape the therapy and continue growing.

My research projects focus on identifying and studying the possible drug-resistance mechanisms that developed during mono-targeted cancer therapies. The outcome of the research can be used to develop better therapeutic approaches with alternative drug or drug combination that blocks the drug-resistance pathways and restore sensitivity to the original drug, in order to overcome drug resistance.

I hope that the knowledge that gained from my research projects can be translated from bench to clinic and benefits the cancer patients.

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Wang

Cun Wang

Postdoctoral Fellow

Experience

I got my PhD in Biochemistry at Fudan University in China, after that I spent three years as a research assistant in the group of Dr. Wenxin Qin at Shanghai Cancer Institute working on liver cancer metastasis.

 

I joined the group of Dr. Bernards as a post-doc in January 2016. My work will be mainly focused on the mechanisms of cellular senescence by performing large-scale and high-throughput genomics technologies.

 

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Research updates View All Updates

  • Award Acadamy Hoogleraren KNAW 2013

    The Academy confers two separate Academy Professor Prizes a year, one to a researcher in the social sciences or humanities, and the other to a researcher in the natural, technical or life sciences. The Prize is intended as a lifetime achievement award for researchers who are between 54 and 59 years of age and regarded as world-class in their field.

    René Bernards is a molecular oncologist at the Netherlands Cancer Institute (Amsterdam) and a part-time professor of molecular carcinogenesis at Utrecht University. Wil Roebroeks is a professor of archaeology at Leiden University. Both researchers will receive the sum of EUR 1 million, which they can use at their discretion to fund scholarly or scientific research.

    The Ministry of Economic Affairs makes a contribution towards the prize. The two recipients were selected by an international jury appointed by the Royal Academy. The Prizes is awarded on Thursday 27 June at the Academy's Trippenhuis Building in Amsterdam.

    Award Academy Professor 2013 KNAW
  • KWF Prize - Queen Wilhelmina Research Prize 2012

    Rene Bernards was awarded the Queen Wilhelmina Research Prize of EUR 2 million from the Dutch Cancer Society (January 29, 2013)

    KWF - Queen Wilhelmina Research Prize 2012

Key publications View All Publications

  • A gene-expression signature as a predictor of survival in breast cancer

    New England J. Med. 2002; 347: 1999-2009

    Van de Vijver, M.J., He, Y.D., van 't Veer, L.J., Dai, H., A M Hart, A.A.M., Voskuil, D., Schreiber, G.J., Peterse, J.L., Roberts, C., et al.

    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

  • Drug therapy: Exploiting synthetic lethality to improve cancer therapy

    Nat Rev Clin Oncol. 2017 Jun;14(6):331-332

    Brunen D, Bernards R

    link to PubMed
  • A Functional Genetic Screen Identifies the Phosphoinositide 3-kinase Pathway as a Determinant of Resistance to Fibroblast Growth Factor Receptor Inhibitors in FGFR Mutant Urothelial Cell Carcinoma

    Eur Urol. 2017 Jan 17

    Wang L, Šuštić T, Leite de Oliveira R, Lieftink C, Halonen P, van de Ven M, Beijersbergen RL, van den Heuvel MM, Bernards R, van der Heijden...

    Link to PubMed
 

Contact

  • Office manager

    Patty Lagerweij

  • E-mail

    p.lagerweij@nki.nl

  • Telephone Number

    +31 20 512 6973

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