Research

About our research

The 3- and 4-dimensional layouts of chromatin play important roles in the establishment of gene expression programs that govern cell fate decisions. We are addressing the following questions:

  • How do changes in 3D chromatin conformation regulate adipose differentiation and function?
  • How do lamin mutations causing lipodystrophies affect chromatin architecture?
  • How do sugars and fatty acids regulate transcription?
  • How does histone H3.3 regulate nuclear architecture?
  • How do cells regulate integrity of the nuclear envelope?

Our work combines molecular, genomics, imaging and computational modeling approaches using patient cells and engineered stem cells.

 Our 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) 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 adipocyte differentiation (Boquest 2007 Stem Cells; Sørensen 2010 Mol Biol Cell; Shah 2014 BMC Genomics)
  • chromatin dynamics during adipogenic differentiation, including lamina-chromatin interactions (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; Paulsen 2019 Nature Genet)
  • deposition of histone variant H3.3 into chromatin (Delbarre 2010 Mol Biol Cell; Delbarre 2013 Genome Res; Ivanauskiene 2014 Genome Res: Delbarre 2017 Genome Res; Udugama 2018 PNAS [Lee Wong lab, Monash U])
  • computational 3D genome modeling (Paulsen 2017 Genome Biol; Paulsen 2018 Nature Protoc)

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  • Histone H3.3 and chromatin homeostasis

    Histone H3.3 and chromatin homeostasis

    We study pathways of H3.3 incorporation into chromatin and how H3.3 contributes to the maintenance of heterochromatin states. We also examine the impact of H3.3 mutations on genome and nuclear organization in pediatric glioblastomas (DIPGs).

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  • Regulation of transcription by sugars and fatty acids

    Regulation of transcription by sugars and fatty acids

    We examine how fatty acids and glucose regulate gene expression through the transcription regulators SHREB and LXR.

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  • Computational 3D genome modeling

    Computational 3D genome modeling

    We develop computational methods for 3D and 4D modeling of genome structure to characterize relationships between 3D chromatin architecture and epigenetic states during differentiation and in cancer cells.

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  • Nuclear lamins & adipose tissue regulation

    Nuclear lamins & adipose tissue regulation

    We are studying how the nuclear lamina regulates spatial chromatin organization and gene expression during adipose stem cell differentiation and in lipodystrophic laminopathies.

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  • Nuclear integrity and genome stability

    Nuclear integrity and genome stability

    We investigate mechanistic and spatiotemporal processes that control nuclear integrity and their contribution to genome stability.

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