Genome organization in laminopathies

  • Project leader:Dr. Julia Madsen-Østerbye
  • Info:Mutations in the lamin A (LMNA) gene, encoding nuclear lamin A/C, cause laminopathies, including familial partial lipodystrophies of Dunnigan type (FPLD2). Partial lipodystrophies affect adipose tissue in a depot-specific manner and leads to severe metabolic complications. Using patient-derived cells and engineered adipose stem cells expressing LMNA mutants, we investigate how FPLD2-causing LMNA mutations deregulate genome and chromatin architecture and function. Other mutations in the LMNA gene cause muscle dystrophies. We also explore how such mutations affect chromatin organization in models of myogenic differentiation. We combine cell biology, microscopy, proteomics and genomics approaches.

Project participants

Julia Madsen-Østerbye, Kristin Vekterud, Nolwenn Briand, Mohamed Abdelhalim (bioinformsatics)

Collaborations with Giovanna Lattanzi, CMR University of Bologna; Gisèle Bonne, INSERM and Hôpital Pitié-Salpétrière, Paris; Nils Krietenstein, Danish Cancer Institute, Copenhagen; Rasmus Siersbæk, University of Southern Denmark, Odense; Kay Schink, University of Oslo; LMNACardiac (www.lmnacaardiac.org); University of Oslo GrowthHouse.

Ongoing research

  • Impact of FPLD2-causing lamin A mutations on functional chromatin organization during adipogenesis
  • Impact of lamin A mutations on nuclear envelope integrity
  • De-regulation of chromatin at the nuclear periphery by lamin A mutations causing lipodystrophies and muscle dystrophies

Recent achievements