Irina Dudanova

FM | Center for Anatomy (UoC)

Prof. Dr. Irina Dudanova CECAD Cologne
Prof. Dr. Irina Dudanova

Principal Investigator

Research Areas

2
3

Molecular Neurodegeneration

Our group focuses on deciphering molecular and circuit mechanisms of neurodegenerative disorders such as Huntington’s disease and Alzheimer’s disease.

Research Focus

Neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease and Huntington’s disease are age-dependent, so far incurable disorders that are becoming increasingly prevalent in our society. At the cellular level, these diseases are characterized by progressive dysfunction and ultimate loss of neurons. Another common hallmark of neurodegenerative disorders is misfolding and aggregation of certain proteins such as Aβ, Tau, α-synuclein or mutant Huntingtin. Previous work from our group investigated the effects of protein aggregates on protein homeostasis (proteostasis) in neurons, as well as on the activity of neuronal networks. However, it remains unclear why certain populations of neurons are particularly vulnerable to degeneration, while other neurons in their vicinity remain largely intact; which molecular mechanisms underlie these differences in vulnerability, and how this affects the function of neural circuits. We tackle these questions with the help of cell culture and genetic mouse models, using a combination of molecular and histological approaches, behavioral analyses and in vivo imaging.

Our team is investigating pathological mechanisms of neurodegenerative diseases. Our goal is to identify molecular pathways and neural circuit defects that play a role in neuronal vulnerability and could provide targets for new therapies.

Our Goals

  • First, we aim to understand the interactions between different cell types and the non cell-autonomous effects in the context of the diseased brain. How do the primarily vulnerable cells influence their initially unaffected synaptic partners? And how does the demise of the vulnerable cell types impact on the structure and function of the respective neural circuits and ultimately cause behavioral deficits? To address these questions, we are using specific Cre lines to gain access to distinct cell types (Voelkl et al., 2022) and perform chronic in vivo imaging (Burgold et al., 2019). In addition, we plan to perform neuroanatomical viral tracings to assess disease-related changes in neuronal connectivity.
     
  • Second, we aim to uncover the molecular mechanisms that make neurons susceptible or resistant to degeneration, with an emphasis on proteostasis pathways. To this end, we are using the Fluc-EGFP reporter (Blumenstock et al., 2021) (Figure 1) to study responses to protein misfolding in different neuronal cell types in mouse disease models. In parallel, we employ unbiased systems approaches including single-nucleus RNA-sequencing to detect molecular programs underlying neuronal resilience. These studies are complemented with mechanistic follow-ups in primary neurons and mouse disease models. 
     
  • Based on these approaches, our ultimate aim is to identify molecular pathways and neural circuit elements with key roles in pathogenesis, in order to design targeted disease-modifying strategies (e.g. Voelkl et al., 2023).

Key Publications


  1. Voelkl K, Gutiérrez-Ángel S, Keeling S, Koyuncu S, da Silva Padilha M, Feigenbutz D, Arzberger T, Vilchez D, Klein R, Dudanova I (2023) Neuroprotective effects of hepatoma-derived growth factor in models of Huntington's disease. Life Sci Alliance 6(11) e202302018. doi: 10.26508/lsa.202302018
  2. Voelkl K, Schulz-Trieglaff EK, Klein R, Dudanova I (2022) Distinct histological alterations of cortical interneuron types in mouse models of Huntington’s disease. Front Neurosci 16. doi: 10.3389/fnins.2022.1022251
  3. Riera-Tur I, Schaefer T, Hornburg D, Mishra A, da Silva Padilha M, Fernández-Mosquera L, Feigenbutz D, Auer P, Mann M, Baumeister W, Klein R, Meissner F, Raimundo N, Fernández-Busnadiego R, Dudanova I (2022) Amyloid-like aggregating proteins cause lysosomal defects in neurons via gain-of-function toxicity. Life Sci Alliance 5(3) e202101185. doi: 10.26508/lsa.202101185
  4. Blumenstock S, Schulz-Trieglaff EK, Voelkl K, Bolender A-L, Lapios P, Lindner J, Hipp MS, Hartl FU, Klein R, Dudanova I (2021) Fluc-EGFP reporter mice reveal differential alterations of neuronal proteostasis in aging and disease. EMBO J, e107260. doi: 10.15252/embj.2020107260
  5. Burgold J, Schulz-Trieglaff EK, Voelkl K, Gutiérrez-Ángel S, Bader JM, Hosp F, Mann M, Arzberger T, Klein R, Liebscher S, Dudanova I (2019) Cortical circuit alterations precede motor impairments in Huntington’s disease mice. Sci Rep9(1):6634. doi: 10.1038/s41598-019-43024-w
Prof. Dr. Irina Dudanova CECAD Cologne
Prof. Dr. Irina Dudanova

Principal Investigator

Research Areas

2
3