Neuroscience

Team TNA: Tau-mediated neurodegeneration in Alzheimer’s disease

Alzheimer’s disease is the most common form of dementia worldwide, affecting millions of patients, with no therapeutic options available to date. While amyloid plaques have long been recognized as hallmarks of the disease, recent evidence suggests that abnormal post-translational modifications of the Tau protein are strongly involved in disease manifestation and progression. In Alzheimer’s disease, Tau is unable to perform its normal function in the stabilization of microtubules and is prone to hyperphosphorylation, aggregation and secretion.

We study the network of Tau post-translational modifications, interactions between different types of modifications, and their impact on Tau function and dysfunction in the disease state using materials obtained from sporadic Alzheimer’s disease patients as well as neurons derived from induced pluripotent stem cells. Analytical and biochemical approaches and screening methods are used to identify tractable therapeutic targets in Tau post-translational modification pathways that can serve as starting points for the development of therapeutic agents. We aim to define a characteristic signature of pathologic Tau post-translational modifications that will serve as a biomarker to support the diagnosis and monitor the progression of Alzheimer’s disease.

Mentors

  • Dr. Laura Gasparini
    Scientific Director Translational Pharmacology, AbbVie (Industry mentor)
  • Dr. Martin Fuhrmann
    Group Leader, German Center for Neurodegenerative Diseases (DZNE), Bonn (Academic mentor)

Publications

    1. Ercan E, Eid S, Weber C, Kowalski A, Bichmann M, Behrendt A, Matthes F, Krauss S, Reinhardt P, Fulle S, Ehrnhoefer DE.
      A validated antibody panel for the characterization of tau post-translational modifications.
      Molecular Neurodegeneration. 2017
    2. Schöndorf DC, Elschami M, Schieck M, Ercan-Herbst E, Weber C, Riesinger Y, Kalman S, Steinemann D, Ehrnhoefer DE.
      Generation of an induced pluripotent stem cell cohort suitable to investigate sporadic Alzheimer’s Disease.
      Stem Cell Res. 2018
    3. Behrendt A, Bichmann M, Ercan-Herbst E, Haberkant P, Schöndorf DC, Wolf M, Fahim SA, Murolo E, Ehrnhoefer DE.
      Asparagine endopeptidase cleaves tau at N167 after uptake into microglia.
      Neurobiol Dis. 2019
    The research of this team is kindly sponsored by AbbVie.

    Our Team Members

    Dr. Dagmar Ehrnhöfer

    Group Leader

    Previous work
    • 2012–2015: Research Associate with Prof. Michael Hayden, University of British Columbia, Vancouver, Canada
    • 2007–2012: Postdoctoral researcher with Prof. Michael Hayden, University of British Columbia, Vancouver, Canada
    • 2001–2007: PhD with Prof. Erich Wanker, Max-Delbrück-Centre for Molecular Medicine in Berlin, Germany
    • Erwin Schrödinger Fellowship of the Austrian Science Fund (FWF)
    • Fellowship of the Canadian Institutes for Health Research (CIHR)

    Dr. Ebru Ercan-Herbst

    Postdoctoral Researcher

    Previous work
    • 20112015: Postdoctoral researcher in neuroscience with Mustafa Sahin, MD, PhD, Dept. of Neurobiology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA. Neuron-oligodendrocyte interactions and myelination in autism spectrum disorders
    • 20062011: PhD in cell biology and biochemistry with Dr. Matthias Seedorf, University of Heidelberg, Center for Molecular Biology, Heidelberg, Germany. Unconventional trafficking of proteins
    • 20042006: Master of Science in Molecular Bioengineering, Technical University of Dresden. Thesis work at the Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany

    Dr. David Schöndorf

    Postdoctoral Researcher

    Modeling neurodegenerative disorders using hiPSCs and gene editing techniques

    Previous work
    • 2004-2009: Diploma (FH) Biochemistry, University of Applied Sciences Mannheim, Germany, Thesis under supervision of Dr. Wilfried Hornberger
    • 2009-2011: Master of Science Neuroscience, University of Tübingen, Germany, Thesis under supervision of Prof. Thomas Gasser
    • 2011-2017: PhD under supervision of Prof. Thomas Gasser, German Center of Neurodegenerative Diseases (DZNE) in Tübingen, Germany

    Maria Bichmann

    Research Associate

    Previous work
    • 20142015: Assistant at the Institute for Instrumental Analytics and Bioanalytics, University of Applied Science in Mannheim, Germany

    • 20132014: Master of Science in Biotechnology with focus on Biomedical Science and Technology, University of Applied Science in Mannheim, Germany

    • 20082012: Bachelor of Science in Biotechnology, University of Applied Science in Esslingen, Germany

    Christian Weber

    Research Associate

    Previous work
    • 2008–2015: Generation, cultivation and differentiation of iPS cells (including lentiviral vector production/cloning), National Center for Tumor Diseases (NCT/DKFZ), Heidelberg, Germany
    • 2005–2008: Training as biology laboratory assistant at Ruprecht-Karls-University, Heidelberg, Germany

    Nuria Prat Oriol

    Master‘s Thesis Student

    Previous work
    • Since 2017: Master of Science in Biotechnology with focus on Biomedical Science and Technology, University of Applied Science in Mannheim, Germany
    • 2012-2016: Bachelor of Science in Biomedical Sciences, University of Barcelona, Spain