Research Group Leader
Research focus: Protein aggregation is a hallmark of many neurodegenerative diseases, but the mechanisms of aggregate toxicity remain incompletely understood. Moreover, it is largely unknown how the demise of the vulnerable neuronal cell types affects the functionality of neural circuits. We address these questions in particular in models of Huntington’s disease, a devastating hereditary movement disorder caused by a CAG repeat expansion in the Huntingtin gene. We work with primary neuronal cultures and mouse disease models, and use cell biological, biochemical and histological methods, as well as behavioural tests and in vivo two-photon imaging. Our goal is to identify molecular pathways and neural circuit impairments that play a role in disease progression and could provide targets for new therapeutic approaches.
Key words: neurodegeneration, protein aggregation, Huntington’s disease, neural circuits, mouse genetics, cell biology, histology, mouse behavior, in vivo imaging.
Burgold, J., Schulz-Trieglaff, E.K., Voelkl, K., Gutiérrez-Ángel, S., Bader, J.M., Hosp, F., Mann, M., Arzberger, T., Klein, R.* Liebscher, S.*, and Dudanova, I.* (2019) Cortical circuit alterations precede motor impairments in Huntington’s disease mice. Sci Rep 2019 Apr 29;9(1):6634. doi: 10.1038/s41598-019-43024-w. *equal contribution
Hosp, F., Gutierrez-Angel, S., Schaefer, M.H., Cox, J., Meissner, F., Hipp, M.S., Hartl, F.U., Klein, R., Dudanova, I.*, and Mann, M. (2017) Spatiotemporal profiling of Huntington’s Dis-ease inclusions reveals widespread loss of protein function. Cell Rep 21: 2291-2303. doi: 10.1016/j.celrep.2017.10.097. *co-corresponding author
Dudanova, I., Klein, R. (2013) Integration of guidance cues: parallel signaling and cross-talk (Review). Trends Neurosci 36: 295-304. doi: 10.1016/j.tins.2013.01.007.
Dudanova, I., Kao, T.-J., Herrmann, J.E., Zheng, B., Kania, A., and Klein, R. (2012) Genetic evidence for a contribution of EphA:ephrinA reverse signaling to motor axon guidance. J Neurosci 32: 5209-5215. doi: 10.1523/JNEUROSCI.5707-11.2012
Dudanova, I., Gatto, G., and Klein, R. (2010) GDNF acts as a chemoattractant to support ephrinA-induced repulsion of limb motor axons. Curr Biol 20: 2150-6. doi: 10.1016/j.cub.2010.11.021.