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Adresse: Otfried-Müller-Straße 10
72076 Tübingen


Gründungs-Direktorin

frontend.sr-only_#{element.icon}: 07071 29-82168
Prof. Julia Skokowa


frontend.sr-only_#{element.icon}: julia.skokowa@med.uni-tuebingen.de


Wissenschaftliche Koordinatorin

frontend.sr-only_#{element.icon}: 07071 29-86013
Dr. Olga Klimenkova


frontend.sr-only_#{element.icon}: Olga.Klimenkova@med.uni-tuebingen.de


AG Schmidt

Dr. rer. nat. Thorsten Schmidt, MME

Dr. rer. nat. Thorsten Schmidt, MME

Institute of Medical Genetics and Applied Genomics

Personenprofil: Mehr zur Person

SCA3 research group

The SCA3 research group focuses on Spinocerebellar Ataxia type 3 (SCA3), also known as Machado-Joseph disease (MJD). SCA3 is an autosomal-dominantly inherited, late onset, neurodegenerative disorder caused by the expansion of a CAG trinucleotide repeat within the ATXN3 gene. This results in an expanded polyglutamine repeat in the encoded ataxin-3 protein. Thus, SCA3 belongs to the group of polyglutamine diseases consisting of other types Spinocerebellar ataxias as well as Huntington's disease. SCA3 is the most common autosomal-dominantly inherited ataxia worldwide. We aim to dissect specific pathomechanims of the disease, to identify novel treatment targets for neurodegenerative disorders and to assess them preclinically in our specific animal models.


List of GRT projects

  • Preclinical assessment of gene therapy approaches
  • Identification of novel treatment strategies and targets


GRT expertise

  • Generation and characterization of transgenic animal models
  • Preclinical testing of treatment strategies


Main GRT methods applied in the lab

  • Behavioural phenotyping of mouse models
  • Generation of cellular assays
  • Biochemical characterization of pathomechanisms
  • Identification of genetics modifiers


Ongoing and requested funding:

Federal Ministry of Education and Research, National Ataxia Foundation, Ataxia UK, German Academic Exchange Service (DAAD), European Commission, Fritz Thyssen Foundation, Deutsche Heredo-Ataxie Gesellschaft e.V. (DHAG) etc.

Publications

  • Pereira Sena P, Weber JJ, Bayezit S, Saup R, Incebacak Eltemur RD, Li X, Velic A, Jung J, Macek B, Nguyen HP, Riess O, Schmidt T. Implications of specific lysine residues within ataxin-3 for the molecular pathogenesis of Machado-Joseph disease. Front Mol Neurosci. 2023 May 19;16:1133271.(DOI: 10.3389/fnmol.2023.1133271)
  • Abeditashi M, Weber JJ, Pereira Sena P, Velic A, Kalimeri M, Incebacak Eltemur RD, Schmidt J, Hübener-Schmid J, Hauser S, Macek B, Riess O, Schmidt T. KPNB1 modulates the Machado-Joseph disease protein ataxin-3 through activation of the mitochondrial protease CLPP. Cell Mol Life Sci. 2022 Jul 6;79(8):401.(DOI: doi: 10.1007/s00018-022-04372-5)
  • Pereira Sena P, Weber JJ, Watchon M, Robinson KJ, Wassouf Z, Hauser S, Helm J, Abeditashi M, Schmidt J, Hübener-Schmid J, Schöls L, Laird AS, Riess O, Schmidt T (2021) Pathophysiological interplay between O-GlcNAc transferase and the 3 Machado-Joseph disease protein ataxin-3. Proc Natl Acad Sci U S A. 118(47):e2025810118. (DOI: 10.1073/pnas.2025810118.)
  • Schmidt J, Mayer AK, Bakula D, Freude J, Weber JJ, Weiss A, Riess O, Schmidt T (2019). Vulnerability of frontal brain neurons for the toxicity of expanded ataxin-3. Hum Mol Genet 28(9):1463-1473. (DOI: 10.1093/hmg/ddy437)
  • Weishäupl D, Schneider J, Peixoto Pinheiro B, Ruess C, Dold SM, von Zweydorf F, Gloeckner CJ, Schmidt J, Riess O, Schmidt T (2019) Physiological and pathophysiological characteristics of ataxin-3 isoforms. J Biol Chem. 294(2):644-661. (DOI: 10.1074/jbc.RA118.005801)
  • Sowa AS, Martin E, Martins IM, Schmidt J, Depping R, Weber JJ, Rother F, Hartmann E, Bader M, Riess O, Tricoire H, Schmidt T (2018). Karyopherin α-3 is a key protein in the pathogenesis of spinocerebellar ataxia type 3 controlling the nuclear localization of ataxin-3. Proc Natl Acad Sci U S A. 115(11):E2624-E2633. (DOI: 10.1073/pnas.1716071115)

Relevant links