Research

About our research

The 3D layout of chromatin plays important roles in the establishment of gene expression programs governing cell fate decisions. We are addressing four main questions:

  • What regulates 3D genome conformation during adipose stem cell differentiation?
  • How do laminopathy-causing lamin mutations affect chromatin conformation?
  • How do histone variants contribute to chromatin homeostasis?
  • How do cells regulate the integrity of their nuclear envelope?

Our work combines cell biological, biochemical, genomics and compational modeling approaches using patient material and engineered stem cells.

 The lab’s research history in brief

  • disassembly and reformation of the nuclear envelope (Steen 2000 J Cell Biol; Steen 2001 J Cell Biol; Martins 2003 J Cell Biol)
  • cell and nuclear reprogramming (Håkelien 2002 Nature Biotech; Taranger 2005 Mol Biol Cell; Freberg 2007 Mol Biol Cell)
  • chromatin immunoprecipitation (ChIP) assays for small cell numbers (Dahl 2008 Nature Protoc; 2009 Genome Biol)
  • epigenetic patterning of developmental gene expression (Lindeman 2011 Dev Cell; Andersen 2012 Genome Biol) and of adipose stem cell differentiation (Boquest 2007 Stem Cells; Sørensen 2010 Mol Biol Cell; Shah 2014 BMC Genomics; Rønningen 2015 BBRC)
  • nuclear lamin - chromatin interactions during adipogenic differentiation and in laminopathies (Lund 2013 Genome Res; Lund 2015 Nucl Acids Res; Oldenburg 2014 Hum Mol Genet; Rønningen 2015 Genome Res; Oldenburg 2017 J Cell Biol; Briand 2018 Hum Mol Genet)
  • mechanisms of deposition of histone H3 variants into chromatin (Delbarre 2010 Mol Biol Cell; Delbarre 2013 Genome Res; Ivanauskiene 2014 Genome Res: Delbarre 2017 Genome Res)
  • Compuational 3D modeling of the human genome (Paulsen 2017 Genome Biol; Paulsen 2018 Nature Protoc)

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  • Nuclear lamins, laminopathies & adipose stem cells

    Nuclear lamins, laminopathies & adipose stem cells

    We are working on identifying determinants of nuclear envelope-chromatin interactions during lineage-specific differentiation and in laminopathy contexts.

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  • Histone variants and chromatin homeostasis

    Histone variants and chromatin homeostasis

    We aim to unveil pathways of loading and incorporation of H3.3 into chromatin, and determine how H3.3 contributes to the maintenance of heterochromatin states in the genome. We also aim to understand the impact of DIPG H3.3 mutations on genome and nuclear organization in pediatric glioblastomas.

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  • Nuclear integrity and genome stability

    Nuclear integrity and genome stability

    Nuclear integrity and genome stability Project leader: Coen Campsteijn The nuclear envelope (NE) constitutes the physical barrier that compartmentalizes the nucleus and protects the genome from damage. However, nuclear compartmentalization is compromised under various conditions, the classical example of which is the open mitosis of many metazoans. More recently, interphase…

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  • 3D genome modeling

    3D genome modeling

    We are developing new computational methods for 3D and 4D modeling of genome structure to characterize relationships between 3D chromatin folding patterns, nuclear envelope-chromatin interactions and epigenetic states during lineage-specific differentiation.

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