Dr. Dorothee Dormann

Research focus: Our research is focused on the role of two RNA-binding proteins, FUS and TDP-43, in the pathogenesis of the neurodegenerative diseases ALS (amyotrophic lateral sclerosis) and FTD (frontotemporal dementia). ALS and FTD are currently incurable, and affected patients usually die within a few years of disease onset. FUS and TDP-43 usually reside in the cell nucleus, where they regulate transcription and splicing of numerous target genes. However, in the brains of ALS and FTD patients, FUS and TDP-43 are abnormally deposited in characteristic protein inclusions in the cytosol of neurons and glia cells. In order to understand the pathomechanisms of ALS and FTD, we are studying how FUS and TDP-43 shuttle between the nucleus and cytoplasm, how they are deposited in pathological protein inclusions and what role the two proteins play in the neuronal cytoplasm, specifically in neuronal dendrites.

Key words: Neurodegeneration, RNA-binding proteins, nuclear transport, protein aggregation

GSN students

• Current: Lara Aletta Gruijs da Silva
• Graduated: Dr. Helena Ederle, Dr. Mario Hofweber, Dr. Hilary Wunderlich

Selected publications:

Bowden H, Dormann D. (2016) Altered mRNP granule dynamics in FTLD pathogenesis. J Neurochem. 138 Suppl 1:112-33.

Suárez-Calvet M, Neumann M, Arzberger T, … , Ansorge O, Dormann D, Haass C. (2016) Monomethylated and unmethylated FUS exhibit increased binding to Transportin and distinguish FTLD-FUS from ALS-FUS, Acta Neuropathol. 131(4):587-604

Bentmann E, Haass C and Dormann D. (2013) Stress granules in neurodegeneration – lessons learnt from FUS and TDP-43. FEBS J. 280(18): 4348-70.

Dormann D, Madl T, Valori C, Bentmann E, Tahirovic S, Abou-Ajram C, Kremmer E, Ansorge O, Mackenzie IR, Neumann M and Haass C. (2012) Arginine methylation next to the PY-NLS modulates Transportin binding and nuclear import of FUS. EMBO J. 31(22): 4258-75.

Bentmann E, Neumann M, Tahirovic S, Rodde R, Dormann D and Haass C. (2012) Requirements for stress granule recruitment of Fused in sarcoma (FUS) and TAR DNA-binding protein of 43 kDa (TDP-43). J Biol Chem. 287(27): 23079-94.

Dormann D and Haass C. (2011) TDP-43 and FUS – A nuclear affair. Trends Neurosci. 34(7): 339-348.

Dormann D, Rodde R, Edbauer D, Bentmann E, Fischer I, Hruscha A, Than M, Mackenzie I, Capell A, Schmid B, Neumann M and Haass C. (2010) ALS-associated FUS mutations disrupt Transportin-mediated nuclear transport. EMBO J. 29(16): 2841-57.