Kügler, Sebastian, Dr.
- 1985-1990 Studies of Biology (Zoology, Biochemistry, Microbiology) University of Kiel
- 1990 Diploma thesis (Dept. of Zoology, University of Kiel)
- 1991-1995 Ph.D thesis (Dept. of Medical Molecular Biology, University of Lübeck)
- 1995-1996 Post-Doc (Dept. Med. Mol. Biol, University of Lübeck)
- 1996-2001 Post-Doc / Senior researcher (Dept. of Neurology, University of Tübingen)
- 2001-now Senior researcher Neurodegeneration / LabHead Vector laboratory, Dept. of Neurology, University of Göttingen
Major Research Interests
We aim at understanding how the physiology of the central nervous system (CNS) becomes impaired in neurodegenerative diseases. Etiology and pathology of ageing-related disorders like Parkinson´s (PD) and Alzheimer´s diseases (AD) are still poorly understood, making it difficult to develop therapeutic strategies. Such strategies, however, are in desperate demand in the ageing societies of the western world.
We make use of highly efficient viral vector systems to introduce genetic information into selected CNS target cell populations or to knock-down expression of proteins of interest by RNAi. For example, we generated novel animal models of AD and PD by over-expression of aSynuclein, Tau, APP and their disease-relevant mutants in the rodent brain by adeno-associated viral (AAV) vectors, making it possible to study mechanisms of neurodegeneration not accessible in conventional transgenic mice.
In order to have a more detailed view on neuropathology in living neurons, we express fluorescent sensor proteins in models of neurodegeneration, revealing sub-cellular events impairing neuronal functions well before the cell is prone to degeneration.
Importantly, gene transfer by AAV vectors is effective not only in rodents but also in the primate and even the songbird brain, and can be accomplished in cultured primary brain cells, in organotypic slice cultures as well as in any brain area of interest.
Another pillar of our research lies in the use of viral vectors as gene therapy tools, e.g. for treatment of monogenic disorders, and in technical developments like cell type specific and regulated transgene expression in the brain of rodents and primates.
Homepage Department/Research Group
Selected Recent Publications
- Jaworski T, Dewachter I, Lechat B, Croes S, Termont A, Demedts D, Borghgraef P, Devijer H, Filipkowski R, Kazmarek L, Kügler S, van Leuven F (2009) AAV-Tau mediates pyramidal neurodegeneration by cell-cycle re-entry without neurofibrillary tangles in wild-type mice. PLOS ONE, 4(10), e7280
- Karpinar DP*, Balija MBG *, Kügler S *, Opazo F, Razaei-Ghaleh N, Bender N, Kim HJ, Taschenberger, G, Falkenburger BJ, Heise H, Kumar A, Riedel D, Fichtner L, Voigt A, Braus GH, Giller K, Becker S, Herzig, A, Baldus M, Jäckle H, Eimer S, Schulz JB, Griesinger C, Zweckstetter M (2009) Pre-fibrillar a-Synuclein variants with impaired ß-structure increase neurotoxicity in Parkinson´s Disease models. EMBO J. 28: 3256 – 3268 (* equal contribution)
- Mironov, S., Skorova, E., Hartelt, N., Mironova, L., Hasan, MT., Kügler, S. (2009) Remodelling of the respiratory network in a mouse model of Rett syndrome depends on BDNF regulated slow calcium buffering. J. Physiol. 587: 2473-2485
- Chen J, Wu J, Apostolova A, Skup M, Irintchecv A, Kügler S *, Schachner M * (2007) Adeno-associated virus-mediated adhesion molecule L1 expression promotes functional recovery after spinal cord injury. Brain 130: 954 – 969 (* equal contribution)
- Kügler S, Hahnewald R, Garrido M, Reiss J (2007) Long-term rescue of lethal inherited disease by AAV-mediated gene transfer in a mouse model of molybdenum cofactor deficiency. Am J Hum Genet 80: 291 – 297
- Shevtsova Z, Malik JMI, Garrido M, Schöll U, Bähr M, Kügler S (2006) Potentiation of in vivo neuroprotection by Bcl-Xl and GDNF co-expression depends on post-lesion time in deafferentiated CNS neurons in vivo. Gene Ther 13: 1569 – 1578
- Malik JMI, Shevtsova Z, Bähr M, Kügler S (2005) Long-term in vivo inhibition of CNS neurodegeneration by Bcl-X-L gene transfer. Mol Ther 11: 373-381