Contact
Johannes Gutenberg-Universität Mainz, Biozentrum
Further Information
Primary research focus: Biomedical Neuroscience
Second research focus: Molecular & Developmental Neuroscience
Third research focus: Cellular & Systems Neuroscience
Keywords: Neurodegeneration, intracellular transport, protein aggregation, ALS, FTD
Brief research description: The Dormann lab's research is focused on the role of RNA-binding proteins in neurodegenerative diseases, especially amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). We are especially interested in two nuclear RNA-binding proteins (FUS and TDP-43), which are genetically linked to ALS and FTD and accumulate in aberrant cytoplasmic aggregates in the brains of ALS and FTD patients. The group's previous work has established that neurodegeneration in ALS/FTD patients is driven by defects in 1) nucleocytoplasmic transport 2) phase separation and 3) post-translational modifications of disease-linked RNA-binding proteins. Using biochemical and cell biological approaches, the Dormann group investigates how these three mechanisms are normally regulated and how they are disturbed in disease.
GSN students:
Current: Lara Aletta Gruijs da Silva
Graduated: Dr. Helena Ederle, Dr. Mario Hofweber, Dr. Hilary Wunderlich
Selected publications:
Ederle H, Funk C, Abou-Ajram C, Hutten S, Funk EBE, Kehlenbach R, Bailer S, Dormann D#. Nuclear egress of TDP-43 and FUS occurs independently of Exportin-1/CRM1, Scientific Reports 8(1):7084 (2018) (doi: 10.1038/s41598-018-25007-5)
Hofweber D*, Hutten S*, Bourgeois B, Spreitzer E, Niedner-Boblenz A, Schifferer M, Ruepp MD, Simons M, Niessing D, Madl T, Dormann D#. Phase separation of FUS is suppressed by its nuclear import receptor and arginine methylation. Cell 173:706–719 (2018) (doi: 10.1016/j.cell.2018.03.004)
Suárez-Calvet M, Neumann M, Arzberger T, Abou-Ajram C, Funk E, Hartmann H, Edbauer D, Kremmer E, Göbl C, Resch M, Bourgeois B, Madl T, Reber S, Jutzi D, Ruepp MD, Mackenzie IR, Ansorge O, Dormann D#, Haass C#. Monomethylated and unmethylated FUS exhibit increased binding to Transportin and distinguish FTLD-FUS from ALS-FUS. Acta Neuropathol 131:587-604 (2016) (doi: 10.1007/s00401-016-1544-2)
Dormann D#, Madl T, Valori C, Bentmann E, Tahirovic S, Abou-Ajram C, Kremmer E, Ansorge O, Mackenzie IR, Neumann M, Haass C#. Arginine methylation next to the PY-NLS modulates Transportin binding and nuclear import of FUS. EMBO J 31:4258-75 (2012) (doi: 10.1038/emboj.2012.261)
Dormann D, Rodde R, Edbauer D, Bentmann E, Fischer I, Hruscha A, Than M, Mackenzie I, Capell A, Schmid B, Neumann M, Haass C. ALS-associated FUS mutations disrupt Transportin-mediated nuclear transport. EMBO J 29:2841-57 (2010) (doi: 10.1038/emboj.2010.143)