Prof. Dr. Dieter Edbauer

Primary research focus: Biomedical Neuroscience

Second research focus: Molecular & Developmental Neuroscience

Third research focus: Cellular & Systems Neuroscience

Keywords: neurodegeneration, ALS, FTD, C9orf72, translation

Research methods: cell culture: primary neurons and iPSC derived patient neurons, lentiviral transduction, imaging, shRNA, CRISPR mouse models: behavior experiments, active and passive vaccination, drug repurposing, single cell sequencing patient material: biomarkers, histology biochemistry and molecular biology: protein and RNA biology, proteomics, RNAseq eager to try new methods

Brief research description:
My lab studies the cell biology of neurodegenerative diseases focusing amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). We aim to replicate all our findings in patient material. We discovered the unconventional translation of the expanded repeat upstream of the C9orf72 coding region into aggregating dipeptide repeat (DPR) proteins. Now I work towards bringing this discovery to clinical application. Currently, we focus on immunotherapy and small molecules. We analyze the role of DPR proteins in ALS and FTD pathogenesis using biochemistry, cell biology, neuropathology and biomarker studies and develop DPR-targeted therapies in our C9orf72 mouse models. In parallel, we explore downstream pathways shared with sporadic ALS/FTD to identify broadly applicable targets.

Supervision of current or graduated GSN PhD students (PhD projects only):
Dr. Bahram Khosravi,  Eszter Katona, Francesca Simonetti

Supervision of GSN MSc/Fast track students:
Ali Rezaei, Linnea Ransom

Selected publications:

Mori K, Weng SM, Arzberger T, May S, Rentzsch K, Kremmer E, Schmid B, Kretzschmar HA, Cruts M, Van Broeckhoven C, … Haass C*, Edbauer D* (2013) The C9orf72 GGGGCC repeat is translated into aggregating dipeptide-repeat proteins in FTLD/ALS. Science 339: 1335-1338 Doi 10.1126/science.1232927

Schludi MH, May S, Grasser FA, Rentzsch K, Kremmer E, Kupper C, T. K, Degeneration GCfFL, Alliance BBB, Arzberger T*, Edbauer D* (2015) Distribution of dipeptide repeat proteins in cellular models and C9orf72 mutation cases suggests link to transcriptional silencing. Acta Neuropathol 130: 537-555 Doi 10.1007/s00401-015-1450-z.

Guo Q, Lehmer C, Martinez-Sanchez A, Rudack T, Beck F, Hartmann H, Perez-Berlanga M, Frottin F, Hipp MS, Hartl FU, Edbauer D*, Baumeister W*, Fernandez-Busnadiego R* (2018) In Situ Structure of Neuronal C9orf72 Poly-GA Aggregates Reveals Proteasome Recruitment. Cell 172: 696-705 e612 Doi 10.1016/j.cell.2017.12.030.

Zhou Q, Mareljic N, Michaelsen M, Parhizkar S, Heindl S, Nuscher B, Farny D, Czuppa M, Schludi C, Graf A, … Edbauer D* (2020) Active poly-GA vaccination prevents microglia activation and motor deficits in a C9orf72 mouse model. EMBO Mol Med 12: e10919 Doi 10.15252/emmm.201910919.

Czuppa M, Dhingra A*, Zhou Q, Schludi C, Konig L, Scharf E, Farny D, Dalmia A, … Heutink P, Edbauer D* (2022) Drug screen in iPSC-Neurons identifies nucleoside analogs as inhibitors of (G4C2)n expression in C9orf72 ALS/FTD. Cell Rep 39: 110913 Doi 10.1016/j.celrep.2022.110913