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Molecular Genetics: Maarten van Lohuizen

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Maarten van Lohuizen, Ph.D ProfessorHead of Division, Group Leader

About Maarten van Lohuizen

Research interest

Role of Polycomb-Group genes in transcriptional repression, stem cell fate and tumorigenesis.
Our lab has a long-standing interest in epigenetic gene regulation dictated by chromatin modifications. We study the mechanism of stable inherited transcriptional repression by Polycomb-group (Pc-G) protein complexes, and the effects of deregulation of Pc-G genes on development, cell cycle control, cancer formation and stem cell maintenance.Currently, the lab uses two model organisms, namely mouse (Mus musculus) and fly (Drosophila melanogaster).

Retroviral insertional mutagenesis & Cancer genomics
Slow transforming retroviruses, such as the Moloney murine leukemia virus (M-MuLV), induce tumors upon infection of a host after a relatively long latency period. These retroviruses can transform the infected host cells through the accidental insertion of their proviruses into the host genome in the vicinity of genes that can confer growth advantages to cells. This means that the proviral insertions found in tumors induced by retroviral insertional mutagenesis mark genes contributing to the tumorigenic process. Since cancer is a complex multistep process, the proviral insertions in one clone of tumor cells also represent oncogenic events that co-operate in tumorigenesis. Novel advances, such as the launch of the complete mouse genome, high-throughput isolation of proviral flanking sequences, new dedicated bioinformatic tools and genetically modified animals have revolutionized proviral tagging into an elegant and efficient approach to identify signaling pathways that collaborate in cancer. This project is executed together with Anton Berns in our department. We have made much progress in the last years and identified over 600 putative oncogenes and tumor suppressor genes and how they cooperate in specific genetic networks. This project is yielding an unexpected wealth of information on haploinsufficient tumor suppressor genes and specific cooperation of oncogenes. It also appears to validate and complement large-scale sequencing efforts of cancer genomes.

Co-workers

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Elisabetta Citterio, Ph.D

Associate staff scientist, VIDI fellow

Experience

The focus of my research is to understand how human cells counteract DNA damage and maintain the integrity of their genome, a condition that is crucial in preventing cancer. In particular, we are studying how the packaging of DNA into chromatin regulates DNA damage signalling/repair and how deregulation of such mechanisms impacts on tumorigenesis and on stem cell maintenance.

After my PhD in DNA repair at the Erasmus University Rotterdam and a postdoc at IFOM, Milan, on chromatin ubiquitination, in 2006 I joined the NKI. Here, I expanded my expertise in the direction of mouse models for cancer and stem cell biology. In 2008, I was awarded a VIDI grant from the Netherlands Organization for Scientific Research (NWO), which allowed me to establish my research line.

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Gaurav Pandey, Ph.D.

Postdoctoral Fellow

Experience

I have completed my PhD at Uppsala university, Sweden during which I was involved in investigating the role of long noncoding RNAs in development and diseases. As a postdoctoral fellow, my research interest involves understanding the epigenetic resistance mechanisms operational upon inhibition of poly-comb group of proteins in brain tumors.

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Gayathri Chandrasekaran, Ph.D.

Postdoctoral Fellow

Experience

I completed my B.Tech (Biotechnology)from SASTRA University, India and M.Sc (Biomedical Science) from the University of Amsterdam, The Netherlands. I then embarked on my doctoral studies at the University of Cambridge. In my postdoctoral work, I will study therapeutic responses to Polycomb inhibition in preclinical mouse models of KRAS mutant lung cancer

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Kopparam

Jawahar Kopparam

Postdoctoral Fellow

Experience

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Santiago Gisler,MSc

Ph.D Student

Experience

I am currently investigating the consequences of Polycomb group (PcG) inhibition in tumor cells to uncover novel functions of PcG mediated repression and possible resistance mechanisms. For this I make use of a high throughput, loss-of-function screening strategy in near haploid, human leukemia cell line. By blocking PcG activity by RNAi or pharmacologically, using Bmi1 and Ezh2 inhibitors alone or in combination with other epigenetic inhibitors, I screen for gene functionality capable of bypassing this repression.

 

 

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Danielle Hulsman

Technical staff

Experience

 

 

 

 

 

 

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Research updates View All Updates

Key publications View All Publications

  • Large scale mutagenesis in p19ARF and p53 deficient mice identifies cancer genes and their collaborative networks.

    Cell. 2008; 133, 727-41

    *Uren AG, *Kool J, Matentzoglu K, de Ridder J, Mattison J, van Uitert M, Lagcher L, Sie D, Tanger E, Cox T, Reinders M, Hubbard TJ, et al.

    Link to Pubmed
  • The oncogene and Polycomb-group gene bmi-1 regulates cell proliferation and senescence through the INK4a locus.

    Nature. 1999; 397: 164-68.

    Jacobs JJL, Kieboom K, Marino S, DePinho RA, van Lohuizen M.

    Link to Pubmed
 
 

Recent publications View All Publications

  • PRC1 coordinates timing of sexual differentiation of female primordial germ cells.

    Nature. 2013; 495: 236-40.

    Yokobayashi S, Liang CY, Kohler H, Nestorov P, Liu Z, Vidal M, van Lohuizen M, Roloff TC, Peters AH.

    Link to pubmed
  • The emerging role of Polycomb repressors in the response to DNA damage.

    J Cell Sci. 2012; 125: 3939-48.

    Vissers JH, van Lohuizen M, Citterio E.

    Link to Pubmed
 

Contact

  • Office manager

    Marij Degen

  • E-mail

    m.degen_AT_ nki.nl

  • Telephone Number

    +31 (0)20 512 9134

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