German Cancer Research Centre - DKFZ
Our research is focused on the question how the structural organization of cells relates to their distinct cell-type specific functions within tissues and organs. In particular, the notion that the shape and sub-structure of cells is severely altered in the transformed state was the starting point for a broad research on what was originally called the cytoskeleton. The cytoskeleton of metazoan cells is established by the coordinated action of three unique filament systems: microtubules, f-actin and intermediate filaments. Their interaction with one another and with cellular organelles is mediated by motor proteins as well as “associated” proteins of various functions. Via a very complex intra-cellular “junctional” organization, the nuclear envelope, the cytoskeleton is directly and physically coupled to chromatin. Here in particular, the nuclear lamina is a major element in coordinating both the mechanical properties of the nucleus as well as the regulation of gene expression and genome maintenance both during embryonic development and later in life in differentiated tissues. Mutations in various components of the nuclear envelope, in particular those of lamin A, have been demonstrated to cause severe diseases such as cardiomyopathy and premature ageing. Recent findings indicate that the nuclear lamina may have an important role in cancer development.
Ramm B, Stigler J, Hinczewski M, Thirumalai D, Herrmann H, Woehlke G, Rief M Sequence-resolved free energy profiles of stress-bearing vimentin intermediate filaments. Proc. Natl. Acad. Sci. USA (2014) 111, 11359-11364.
Solovei I, Wang AS, Thanisch K, Schmidt CS, Krebs S, Zwerger M, Cohen TV, Devys D, Foisner R, Peichl L, Herrmann H, Blum H, Engelkamp D, Stewart CL, Leonhardt H, Joffe B. LBR and lamin A/C sequentially tether peripheral heterochromatin and inversely regulate differentiation. Cell (2013) 152, 584-598.
Chernyatina AA, Nicolet S, Aebi U, Herrmann H, Strelkov SV. Atomic structure of the vimentin central α-helical domain and its implications for intermediate filament assembly. Proc. Natl. Acad. Sci. U S A (2012) 109, 13620-13625. Kolb T, Maass K, Hergt M, Aebi U, Herrmann H. Lamin A and lamin C form homodimers and coexist in higher complex forms both in the nucleoplasmic fraction and in the lamina of cultured human cells. Nucleus (2011) 2, 425-433.
Kapinos LE, Schumacher J, Mücke N, Machaidze G, Burkhard P, Aebi U, Strelkov SV and Herrmann H. Characterization of the head-to-tail overlap complexes formed by human lamin A, B1 and B2 "half-minilamin" dimers. J. Mol. Biol. (2010) 396, 719-731.
Portet S, Mücke N, Kirmse R, Langowski J, Beil M, and Herrmann H. Vimentin intermediate filament formation: In vitro measurement and mathematical modeling of the filament length distribution during assembly. Langmuir (2009) 25, 8817-8823.
Foeger, N., Wiesel, N., Lotsch, D., Mücke, N., Kreplak, L., Aebi, U., Gruenbaum, Y. and Herrmann H. Solubility properties and specific assembly pathways of the B-type lamin from Caenorhabditis elegans. J. Struct. Biol. (2006) 155, 340-350.
Bär, H., Mücke, N., Sjöberg, G., Aebi, U. and Herrmann, H. Severe disease-causing desmin mutations interfere with in vitro filament assembly at distinct stages. Proc. Natl. Acad. Sci. USA (2005) 102, 15099-15104.
Mücke, N., Wedig, T., Bürer, A., Marekov, L.N., Steinert, P.M., Langowski, J., Aebi, U. and Herrmann, H. Molecular and biophysical properties of assembly-starter-units of human vimentin. J. Mol. Biol (2004) 340, 97-114.
Strelkov, S.V., Schumacher, J., Burkhard, P., Aebi, U. and Herrmann, H. Crystal structure of the human lamin A coil 2B dimer: Implications for the head-to-tail association of nucler lamins. J. Mol. Biol. (2004) 343, 1067-1080.
Köster S, Weitz D, Goldman RD, Aebi U, and Herrmann H. Intermediate filament mechanics: From coiled coils to filaments, fibers and networks in vitro and in the cell. Curr. Op. Cell Biol. (2014) submitted.
Clemen CS, Herrmann H, Strelkov SV, Schröder R. Desminopathies: pathology and mechanisms. Acta Neuropathol. (2013) 125, 47-75.
Herrmann H, Strelkov SV, Burkhard P, and Aebi U. Intermediate filaments: primary determinants of cell architecture and plasticity. J. Clin. Invest. (2009) 119, 1772-1783.
Herrmann H and Aebi, U. Intermediate filaments: Molecular structure, assembly mechanism, and integration into functionally distinct intracellular scaffolds. Annu. Rev. Biochem. (2004) 73, 749-789.