Dr. Bohr-Gasse 9
Lamins in nuclear organization and human disease
Lamins form a scaffold structure at the nuclear envelope, the lamina, and are also found throughout the nucleoplasm. They determine mechanical properties of the nucleus and are involved in chromatin regulation. Lamin mutations cause human diseases ranging from muscular dystrophy to premature-aging syndromes.
We aim at understanding molecular mechanisms of lamin functions in nuclear organization, mechanosignaling and chromatin regulation during differentiation and their role in diseases.
In particular, we investigate i) how lamin-binding proteins affect lamin dynamics and functions, ii) how these proteins crontrol lamin-chromatin interactions, and iii) how these processes are affected by lamin disease mutations. While lamin-chromatin interactions are known to contribute to stable gene repression during differentiation, we found binding of lamins also to active, open chromatin throughout the nucleus, affecting epigenetic pathways and gene regulation. This activity is changed in cells expressing a progeria premature ageing disease-linked lamin mutant.
A second focus in the lab addresses molecular mechanoresponse pathways causing cardiovascular disease in progeria premature aging disease. In mouse models expressing the lamin disease variant in endothelial cells, we investigate pro-atherogenic changes at the molecular level.
Analysis of nuclear organization and biochemistry of lamins.
Analysis of transgenic mice phenotypes in vivo and in vitro using promary cells.
Lamins in chromatin organizion
Contribution of aged endothelial cells to cardioascular disease in progeria premature aging disease
25–30 May 2020, Spetses Island, Greece