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Gene Regulation: Elzo de Wit

De Wit, Elzo

Elzo de Wit, Junior Group Leader

About Elzo de Wit

Genome function and dynamics

From genotype to phenotype
Technological advances in DNA sequencing have made the €1000 genome a reality. This will usher in an era of personal genomics. One of the key challenges in this burgeoning field will be to understand how genetic variation leads to differences between individuals. Years of human genetics research has identified thousands of genetic regions associated with human traits and disease. Many of these this genetic regions are in non-coding regions of the genome. Predicting the effect of non-coding variation is, compared to coding variants, far from trivial. We have developed tools that allow the linkage of genetic variants on the same chromosome, to create so-called haplotypes. Haplotypes will help us to better predict the effect of a genetic variant on gene expression.

3D organization of the genome
Storage of our DNA inside the nucleus is a formidable task. When stretched out our genome measures 2 meters in length. But it has to fit into a nucleus that is one 100th of a millimeter in diameter. To achieve this the genome is very efficiently folded. It has become clear that the 3D organization of the genome plays an important role in the regulation of genes. We have been at the forefront of the development of tools that analyze how the genome is folded, such as 4C and Hi-C. We continue to develop these tools to better understand the interplay between genome folding and gene expression.

Co-workers

Kuznetsova, Tanyana

Kuznetsova, Tanya

Postdoc

Experience

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Le Huy

Huy Le

Postdoc

Personal details

Groups

Experience

My PhD is on mechanical regulation of stem cell fate decisions. I identified a force-driven transcriptional rheostat that controls chromatin architecture to finetune gene expression, to control lineage progression during epidermal morphogenesis. I am keen on continuing with this line of research to further understand the mechanisms that rely external cellular signal on nucleus and chromatin level. In brief, I want to know how the nuclear envelope and its components control chromatin architecture as well as transcription in order to define cell response and identity.

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Liu Ningquin

Ningqing Liu

Postdoc

Experience

I completed my PhD in a topic of biomarker discovery in breast cancer using mass spectromtery based proteomics, and later on switched to study epigenetic regulation in colorectal cancer. In NKI, my research topics will focus on two projects: (1) study epigenome regulated by important cancer progressive factors, using state-of-the-art next generation sequencing, organoid culture and genomic editing techniques; (2) understand the dynamic regulation of 3D genome and gene transcription in mouse embryonic stem cells by depleting key pluripotent factors.

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Van der Weide, Robin

Robin van der Weide

PhD student

Experience

I started my PhD in 2015 in the lab of Elzo de Wit, where I will be working on a computational framework for linking haplotypes to differences in gene expression.
I finished my master in Cancer, Stem cells and Development at the Utrecht University with honors. My first internship was in the lab of Edwin Cuppen at the Hubrecht Institute, where I looked at often discarded pieces of information from DNA-sequencing. I did my  second internship in Cambridge in the lab of Dave Adams. Here I studied melanoma-predisposition mutation-clusters in the non-coding regions of the genome.

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Teunissen, H.

Hans Teunissen

Technician

Experience

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Rijlaarsdam - Hoekstra, Laura

Laura Rijlaarsdam-Hoekstra

PhD student

Experience

I obtained my bachelor degree in Biology at the University of Amsterdam (UvA) and my master degree in Bioinformatics also at the UvA in combination with the VU university. For the first research project I joined the Biosytems Data Analysis Group. The project involved applying machine learning to predict age from DNA methylation. The resulting model was subsequently used to develop a wet lab protocol for forensic science. The second project was at DSM in the genetics department. I worked with Pacific Biosciences sequence data to characterize DNA methylation in one of their industrially deployed microorganisms.      

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Hazelaar, Sheere

Sheree Hazelaar

master student

Experience

I am currently enrolled at the master programme of Bioinformatics and Systembiology at the Vrije Universiteit where I am specializing in bioinformatics.
At the NKI I am doing a 5-month internship where I will be doing a project on characterizing the effects of genome-wide perturbed chromatin folding on gene expression.

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Key publications View All Publications

  • The pluripotent genome in three dimensions is shaped around pluripotency factors

    Nature. 2013 Sep 12;501(7466):227-31

    de Wit E, Bouwman BA, Zhu Y, Klous P, Splinter E, Verstegen MJ, Krijger PH, Festuccia N, Nora EP, Welling M, Heard E, Geijsen N, Poot et al.

    Link to PubMed
  • CTCF Binding Polarity Determines Chromatin Looping

    Mol Cell. 2015 Nov 19;60(4):676-84

    de Wit E, Vos ES, Holwerda SJ, Valdes-Quezada C, Verstegen MJ, Teunissen H, Splinter E, Wijchers PJ, Krijger PH, de Laat W

    Link to PubMed
 
 

Recent publications View All Publications

  • Cell-of-Origin-Specific 3D Genome Structure Acquired during Somatic Cell Reprogramming

    Cell 2016;18:597-610

    Krijger PHL, Di Stefano B, de Wit E, Limone F, van Oevelen C, de Laat W, Graf T

    Link to PubMed
  • Discovery and validation of sub-threshold genome-wide association study loci using epigenomic signatures

    Elife. 2016 May 10;5

    Wang X, Tucker NR, Rizki G, Mills R, Krijger PH, de Wit E, Subramanian V, Bartell E, Nguyen XX, Ye J, Leyton-Mange J, Dolmatova EV,...

    Link to PubMed
 

Contact

  • Office manager

    Suzanne Corsetto

  • E-mail

    s.corsetto@nki.nl

  • Telephone Number

    +31 20 512 1970

Suzanne Corsetto
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