Clinic of Neurology
Faculty of Medicine
Bergmannsheil University Hospital
Bürkle-de-la-Camp-Platz 1
44789 Bochum
Phone:
+49 (0)234 302-3465
Email:
matthias.vorgerd@ruhr-uni-bochum.de
The scientific focus of our group is in the research field of clinical phenotypes and pathogenesis of hereditary and acquired myopathies. The disease groups which are currently under investigation include the autosomal limb girdle muscular dystrophy (LGMD) and autosomal hereditary myofibrillar myopathy (MFM) and the acquired Inclusion Body Myositis (IBM).
With regard to the MFM and LGMD forms we currently conduct detailed characterizations of the Filamin C-associated molecular pathology with respect to newly identified mutations and detected impairments of the ubiquitin-proteasome system (UPS) and autophagy-mediated protein degradation. These works include transfection of murine myoblast cell lines, characterization of the mutant Filamin C protein and mass spectrometric analysis by laser micro-dissection isolated pathological protein aggregates, as well as the identification and characterization of new and disease-associated Filamin-binding partners.
The central aim of the study of IBM and other vacuolar myopathies is to characterize the proteomic signature in these myopathies. On this basis, specific diagnostic markers for the IBM are checked and validated to distinguish them from other myopathies and myositis.
Our investigations include the histopathology of skeletal and cardiac muscle, special staining, immunofluorescence and double immunofluorescence analysis, laser micro-dissection of muscle tissue and cultured myoblasts / myotubes with sequential proteomic, cell-culture systems with primary and iPSC-derived muscle cells, as well as transient and stable transfections of myoblast cell cultures.
Krause, K., Eggers, B., Uszkoreit, J., Eulitz, S., Rehmann, R., Güttsches, A. K., Schreiner, A., van der Ven, P. F. M., Fürst, D. O., Marcus, K., Vorgerd, M., & Kley, R. A. (2023). Target formation in muscle fibres indicates reinnervation - A proteomic study in muscle samples from peripheral neuropathies. Neuropathology and Applied Neurobiology, 49(1), e12853. https://doi.org/10.1111/nan.12853
Kley, R. A., Leber, Y., Schrank, B., Zhuge, H., Orfanos, Z., Kostan, J., Onipe, A., Sellung, D., Güttsches, A., Eggers, B., Jacobsen, F., Kress, W., Marcus, K., Djinović-Carugo, K., Van Der Ven, P. F., Fürst, D. O. & Vorgerd, M. (2021). FLNC-Associated Myofibrillar Myopathy. Neurology Genetics, 7(3), e590. https://doi.org/10.1212/nxg.0000000000000590
Rehmann, R., Froeling, M., Rohm, M., Forsting, J., Kley, R. A., Schmidt-Wilcke, T., Karabul, N., Meyer-Frießem, C. H., Vollert, J., Tegenthoff, M., Vorgerd, M., & Schlaffke, L. (2020). Diffusion tensor imaging reveals changes in non-fat infiltrated muscles in late onset Pompe disease. Muscle & Nerve, 62(4), 541–549. https://doi.org/10.1002/mus.27021
Rehmann, R., Schlaffke, L., Froeling, M., Kley, R. A., Kühnle, E., Marées, M. de, Forsting, J., Rohm, M., Tegenthoff, M., Schmidt-Wilcke, T., & Vorgerd, M. (2019). Muscle diffusion tensor imaging in glycogen storage disease V (McArdle disease). European Radiology, 29(6), 3224–3232. https://doi.org/10.1007/s00330-018-5885-1
Unger, A., Beckendorf, L., Böhme, P., Kley, R., Frieling-Salewsky, M. von, Lochmüller, H., Schröder, R., Fürst, D. O., Vorgerd, M., & Linke, W. A. (2017). Translocation of molecular chaperones to the titin springs is common in skeletal myopathy patients and affects sarcomere function. Acta Neuropathologica Communications, 5(1), 72. https://doi.org/10.1186/s40478-017-0474-0
Unger, A., Dekomien, G., Güttsches, A., Dreps, T., Kley, R., Tegenthoff, M., Ferbert, A., Weis, J., Heyer, C., Linke, W. A., Martinez-Carrera, L., Storbeck, M., Wirth, B., Hoffjan, S., & Vorgerd, M. (2016). Expanding the phenotype of BICD2 mutations toward skeletal muscle involvement. Neurology, 87(21), 2235–2243. https://doi.org/10.1212/WNL.0000000000003360
Kley, R. A., van der Ven, P. F. M., Olivé, M., Höhfeld, J., Goldfarb, L. G., Fürst, D. O., & Vorgerd, M. (2013). Impairment of protein degradation in myofibrillar myopathy caused by FLNC/filamin C mutations. Autophagy, 9(3), 422–423. https://doi.org/10.4161/auto.22921
Kley, R. A., Hellenbroich, Y., van der Ven, P. F. M., Fürst, D. O., Huebner, A., Bruchertseifer, V., Peters, S. A., Heyer, C. M., Kirschner, J., Schröder, R., Fischer, D., Müller, K., Tolksdorf, K., Eger, K., Germing, A., Brodherr, T., Reum, C., Walter, M. C., Lochmüller, H., . . . Vorgerd, M. (2007). Clinical and morphological phenotype of the filamin myopathy: A study of 31 German patients. Brain : A Journal of Neurology, 130(Pt 12), 3250–3264. https://doi.org/10.1093/brain/awm271
Schulte-Mattler, W. J., Kley, R. A., Rothenfusser-Korber, E., Böhm, S., Brüning, T., Hackemann, J., Steinbrecher, A., Düring, M. V., Voss, B., & Vorgerd, M. (2005). Immune-mediated rippling muscle disease. Neurology, 64(2), 364–367. https://doi.org/10.1212/01.WNL.0000149532.52938.5B
Betz, R. C., Schoser, B. G., Kasper, D., Ricker, K., Ramírez, A., Stein, V., Torbergsen, T., Lee, Y. A., Nöthen, M. M., Wienker, T. F., Malin, J. P., Propping, P., Reis, A., Mortier, W., Jentsch, T. J., Vorgerd, M., & Kubisch, C. (2001). Mutations in CAV3 cause mechanical hyperirritability of skeletal muscle in rippling muscle disease. Nature Genetics, 28(3), 218–219. https://doi.org/10.1038/90050
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Last update: Feb 07, 2024
