Research

About our research

The 3-dimensional layout of the genome together with interactions of chromatin with the nuclear lamina, at the nuclear periphery, play important roles in the establishment of gene expression programs that govern cellular identity.

In adipose tissue, adipocyte progenitors differentiate into white adipocytes which store lipids, and into 'beige' adipocytes which produce heat.  In  this context we are studying:

  • How 3D genome conformation and chromatin-lamina interactions regulate adipogenic cell fate
  • How lamin A mutations causing lipodystrophies impact on nuclear architecture and adipogenesis

In cancer, the epithelial-to-mesenchymal transition (EMT) reflects a transformed and potentially malignant cell state. We are also investigating:

  • How nuclear lamins regulate gene expression programs triggering EMT in models of breast cancer

Our work combines molecular, genomics, microscopy and computational approaches using normal and cancer cell lines, patient cells and stem cells from adipose tissue.

 Our lab’s research history in brief

  • gene expression in constitutive and variable LADs during differentiation (Madsen-Østerbye 2022, in review)
  • lamina-associated domains (LADs) during the circadian cycle (Brunet 2019 Front Genet) and polymer modeling of chromatin-lamina interactions (Brunet 2020 Nucleus)
  • 3D changes in genome conformation during adipogenic differentiation: TAD cliques (Paulsen 2019 Nature Genet; Liyakat Ali 2021 BMC Genomics)
  • FLPD2-causing lamin A mutation and adipogenic deregulation ( Briand 2018 Hum Mol Genet; Oldenburg 2017 J Cell Biol; Oldenburg 2014 Hum Mol Genet)
  • 3D genome modeling (Paulsen 2017 Genome Biol; Paulsen 2018 Nature Protoc); Chrom3D package on github:  https://github.com/Chrom3D/Chrom3D
  • lamina-associated domains (LADs) during adipogenic differentiation (Lund 2013 Genome Res; Lund 2015 Nucl Acids Res; Rønningen 2015 Genome Res); EDD package on github: https://github.com/CollasLab/edd
  • 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)
  • 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; Rønningen 2015 Genome Res)
  • chromatin immunoprecipitation (ChIP) for small cell numbers (Dahl 2008 Nature Protoc; Dahl 2009 Genome Biol)
  • cell and nuclear reprogramming (Håkelien 2002 Nature Biotech; Taranger 2005 Mol Biol Cell; Freberg 2007 Mol Biol Cell)
  • disassembly and reformation of the nuclear envelope (Steen 2000 J Cell Biol; Steen 2001 J Cell Biol; Martins 2003 J Cell Biol)

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  • Regulation of adipocyte development and function by nuclear lamins and chromatin

    Regulation of adipocyte development and function by nuclear lamins and chromatin

    We examine chromatin-linked mechanisms regulating progenitor fate specification in various adipose tissues, as well as white vs. thermogenic beige adipogenesis.

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  • 3D genome conformation

    3D genome conformation

    We combine molecular/cell biology, microscopy imaging and computational 3D genome modeling to identify features of the 3D genome conformation and how these evolve during multilineage stem cell differentiation.

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  • Nuclear architecture in lipodystrophic laminopathies

    Nuclear architecture in lipodystrophic laminopathies

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

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  • Dynamics of the nuclear lamina during differentiation and EMT

    Dynamics of the nuclear lamina during differentiation and EMT

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

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