Research

About our research

The 3-dimensional layout of the genome, including interactions of chromatin with the nuclear lamina at the nuclear periphery, plays an important role in the establishment of gene expression programs that govern lineage-specific differentiation and cell identity. In adipose tissue, adipocyte progenitors (also called adipose stem cells, or ASCs) differentiate into lipid-storing white or energy-dissipating (thermogenic) beige adipocytes, while some white adipocytes are able to convert to beige adipocytes under cold exposure.

• We study how genome conformation and nuclear lamina-chromatin interactions contribute to the regulation of adipose stem cell fate, using a well-established in vitro adipose differentiation system

Laminopathies are lamin-linked diseases that include muscle dystrophies, progeria and partial lipodystrophy of type 2 (FPLD2). Deficiencies in lipid storage capacity of adipocytes in patients with lipodystrophy drastically limit fat tissue expandability and exposes other organs to lipotoxicity. 

• We study how lamin A mutations causing FPLD2 impact nuclear architecture and genome organization during adipogenesis and in adipocytes

Nuclear lamins are also involved in the epithelial-to-mesenchymal transition (EMT) and cancer progression.

• We investigate how lamins regulate gene expression programs triggering EMT

We combine molecular, imaging, genomics and bioinformatics approaches using patient cells, adipose stem cells and cancer cell lines.

 Our lab’s research history in brief

• LncRNA HOTAIR and adipocyte function (Potolitsyna 2022 Sci Reports)
• Euchromatic active regions in lamina-associated domains (LADs) during adipose differentiation (Madsen-Østerbye 2022 Genome Biol)
• LADs during the circadian cycle (Brunet 2019 Front Genet) and modeling of chromatin-lamina interactions (Brunet 2020 Nucleus)
• 3D genome modeling with Chrom3D (Paulsen 2017 Genome Biol; Paulsen 2018 Nature Protoc):  https://github.com/Chrom3D/Chrom3D and TAD cliques during adipose differentiation: (Paulsen 2019 Nature Genet; Liyakat Ali 2021 BMC Genomics)
• FLPD2-causing lamin A mutation deregulates endothelial and adipogenic differentiation (Briand 2018 Hum Mol Genet; Oldenburg 2017 J Cell Biol; Oldenburg 2014 Hum Mol Genet)
• LADs during adipose differentiation (Lund 2013 Genome Res; Lund 2015 Nucl Acids Res; Rønningen 2015 Genome Res); EDD package for LAD detection: https://github.com/CollasLab/edd
• Deposition of histone variant H3.3 into chromatin (Delbarre 2010 Mol Biol Cell, 2013 Genome Res, 2017 Genome Res; Ivanauskiene 2014 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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