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Gene Regulation: Fred van Leeuwen

FredVanLeeuwen.jpg

Fred van Leeuwen, Ph.D professorGroup leader

About Fred van Leeuwen

Research interest

Histone proteins package eukaryotic genomes and carry post-translational modifications. These modifications affect many transactions of the genome and provide a putative epigenetic memory system to transmit information about genome activity from one cell generation to the next. Epigenetic regulators are frequently mutated in cancer and provide appealing opportunities for therapeutic intervention. The Van Leeuwen lab uses genetic approaches to study mechanisms and principles of epigenetic regulation. Our general strategy is to develop new tools and technologies, taking advantage of yeast as a flexible model system. These novel tools enable us to explore new areas of chromatin biology (e.g. histone dynamics). In addition, they also make it possible to address key questions in the field of epigenetics that have traditionally been difficult to address (e.g. epigenetic memory). Finally, genetic engineering strategies in yeast allow us to dissect specific chromatin processes in high molecular detail (e.g. histone methylation). Our research lines are centered around the two main questions outlined below.

How do epigenetic regulators control genome activity and how are the regulators regulated?

Following up on our previous discoveries, we focus on the histone methyltransferase Dot1. Dot1 is conserved from yeast to human and involved in human leukemia caused by rearrangements of the MLL1 gene. By combining genetics, quantitative proteomics and mathematical modeling, and by using yeast as an 'in vivo test tube', we recently obtained a high level of mechanistic understanding of Dot1's methylation mechanism. This information has been instrumental for our current studies. By combining novel barcode-sequencing screens (e.g. Epi-ID) and proteomics studies we are unraveling the mechanisms of regulation of Dot1 and its downstream effects on gene expression and cell function. In parallel to our discovery studies in yeast, we have recently started developing tools in human cells using CRISPR-CAS genome editing strategies and mouse models of cancer to translate our findings in yeast to mammals.

What is epigenetic information, how stable is it, how is it transmitted?

To test hypotheses of epigenetic memory, we take advantage of our tools (e.g. Recombination-Induced Tag Exchange or RITE) to measure histone protein inheritance. We also use these tools to study the function and mechanisms of histone protein turnover, a relatively unexplored but most likely very important layer of epigenetic regulation. In addition, we develop screening strategies to uncover the factors involved in histone turnover or inheritance, with the goal to allow functional studies by perturbation.

Available positions

From time to time we have positions available for PhD students, postdocs, bioinformaticians or technicians. Please send your application and CV to fred.v.leeuwen@nki.nl if you are interested.

Web of Science

Fred van Leeuwen's Publons-page on Web of Science.

Co-workers

Maliepaard, Eliza Marie

Eliza Mari Maliepaard

PhD student

Experience

I obtained both my bachelor and master degree in Biomedical Sciences at the Radboud University in Nijmegen. During my master I performed two research internships in the fields of epigenetics and cancer. I started my PhD at the van Leeuwen group in 2016.

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Thom Molenaar nieuw

Thom Molenaar

PhD student

Experience

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Malik

Muddassir Malik

PhD student

Experience

I obtained a BSc and MSc in Bio-Pharmaceutical Sciences at Leiden University, and specialized in research.

During my MSc I have completed research internships at the department of Rheumatology (LUMC) and the department of Molecular Carcinogenesis (NKI-AvL), during which I obtained more theoretical and experimental knowledge, related to immunology and cancer research.

In May 2019, I started as a PhD student in the group of Fred van Leeuwen. In collaboration with the group of Heinz Jacobs, my project will focus on the epigenetic control of T cells to modulate immune responses.

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Marlize van Breugel

Marlize van Breugel

PhD student

Experience

In 2020 I obtained my master's degree in Life Science & Technology from Leiden University. During my time as a master student, I performed my first internship within the group of Fred van Leeuwen at the NKI to study the epigenetic regulation of retrotransposons in yeast. For my second internship, I moved to Heidelberg, Germany, to study cis-regulatory DNA elements in Drosophila in the group of Justin Crocker at EMBL. Now I'm back at the Van Leeuwen group as a PhD student to continue my research on a novel chromatin binder in yeast. In addition, I will use Epi-Decoder as a tool to study chromatin communication between promoters and gene bodies and possibly translate this tool from yeast to humans.

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Welsem, Tibor van.jpg

Tibor van Welsem

Technician

Experience

I started at the NKI in 1998 and worked in different departments. I studied the classification of hereditary breast tumors with genetic profiles obtained by comparative genomic hybridization.

Since 2004 I am working in the laboratory of Fred van Leeuwen. I participate in several projects and provide support to PhD students and postdocs, for example by developing new tools and reagents and by doing genetic screens. 

 

 

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Maxime Kempers

Maxime Kempers

master student

Experience

I obtained my Bachelor degree in Biology and Medical Laboratory Research at the University of Applied Sciences in Leiden. During my BSc I have performed internships at the department of Immunology, Genetics and Pathology (Rudbecklaboratoriet, Sweden) and the department of Molecular Cell Biology and Immunology (Amsterdam UMC, VUmc). In December 2019, I started my master internship in the group of Fred van Leeuwen to obtain more theoretical and experimental knowledge in the field of epigenetics.

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Key publications View All Publications

  • Direct screening for chromatin status on DNA barcodes in yeast delineates the regulome of H3K79 methylation by Dot1

    eLife, Dec 2016

    Vlaming, H., Molenaar, T. M., van Welsem, T., Poramba-Liyanage, D. W., Smith, D. E., Velds, A., Hoekman, L., Korthout, T., Hendriks, S., Altelaar, A. M. and van Leeuwen, F.

    Link to article
  • Decoding the chromatin proteome of a single genomic locus by DNA sequencing

    PLoS Biol 2018;16(7): e2005542

    Korthout T, Poramba-Liyanage DW, van Kruijsbergen I, Verzijlbergen KF, van Gemert FPA, van Welsem T, et al.

    Link to article
 
 

Recent publications View All Publications

  • Chromatin modified in a molecular reaction chamber.

    Nature. 2020 Mar;579(7800):503-504

    Gilbert N, van Leeuwen F.

    Link to article
  • Application of Recombination-Induced Tag Exchange (RITE) to study histone dynamics in human cells

    Epigenetics, Mar 2020

    Thom M. Molenaar, Marc Pagès-Gallego, Vanessa Meyn & Fred van Leeuwen

    Link to article
 

Contact

  • Office manager

    Suzanne Corsetto

  • E-mail

    s.corsetto@nki.nl

  • Telephone Number

    + 31 20 512 1970

Suzanne Corsetto

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