Functional Genetics of Neurodegeneration and Neurological Disorders Working Group

The Functional Genetics of Neurodegeneration and Neurological Disorders working group, led by Dr. Hans Zempel, PhD, is researching the pathological mechanisms of neurodegenerative and rare genetic neurological diseases. We are working to identify and characterize the factors that influence neuron and synaptic function. Rare genetic diseases often provide information on the development and treatment of age-related diseases, including those of a non-genetic nature - such as Alzheimer’s type dementia.

With the additional support of the CMMC, we use state-of-the-art microscopy, cell biology, genetic and biochemical methods to identify and characterize genetic and non-genetic factors of neurodegeneration of the central and peripheral nervous system.

Our research focuses on the cellular and molecular mechanisms and therapy of

  • Alzheimer’s type dementia and applied related tauopathies, such as Frontotemporal dementias (Pick's disease, corticobasal degeneration, progressive supranuclear paralysis)
  • Mitochondriopathies, such as polymerase gamma mutations
  • Neurological diseases caused by cytoskeletal disorders, cellular transport disorders or neuronal migration disorders (hereditary spastic paraplegia (HSP), lissencephalopathies)
  • 2-hydroxyglutarate aciduria and related syndromes
  • Lysosomal storage disorders
  • Neuronal cell polarity

We welcome initiatives for scientific collaboration and ideas for the treatment of neurodegenerative diseases.

Selected publications

Zempel H, Dennissen FJA, Kumar Y, Luedtke J, Biernat J, Mandelkow EM, Mandelkow E.
Axodendritic sorting and pathological missorting of Tau are isoform-specific and determined by axon initial segment architecture.
J Biol Chem. 2017 Jul 21;292(29):12192-12207. doi: 10.1074/jbc.M117.784702. Epub 2017 May 23.<
PubMed PMID: 28536263

Zempel H, Sadzot B and Haag N.
Treatment Avenues for the Juvenile and Adult Onset Mitochondriopathies Alpers Syndrome, Ataxia Neuropathy Spectrum, MEMSA and PEO Caused by Polymerase-Gamma Mutations Ala467Thr and Trp748Ser.
SM J Neurol Neurosci. 2017; 3(2): 1013. Review.

Zempel H, Mandelkow EM.
Tau missorting and spastin-induced microtubule disruption in neurodegeneration: Alzheimer Disease and Hereditary Spastic Paraplegia.
Mol Neurodegener. 2015 Dec 21;10:68. doi: 10.1186/s13024-015-0064-1. Review.
PubMed PMID: 26691836

Zempel H, Mandelkow E.
Lost after translation: missorting of Tau protein and consequences for Alzheimer disease.
Trends Neurosci. 2014 Dec;37(12):721-32. doi: 10.1016/j.tins.2014.08.004. Epub 2014 Sep 12. Review.
PubMed PMID: 25223701

Zempel H, Luedtke J, Kumar Y, Biernat J, Dawson H, Mandelkow E, Mandelkow EM.
Amyloid-β oligomers induce synaptic damage via Tau-dependent microtubule severing by TTLL6 and spastin.
EMBO J. 2013 Nov 13;32(22):2920-37. doi: 10.1038/emboj.2013.207. Epub 2013 Sep 24.
PubMed PMID: 24065130

Li X, Kumar Y, Zempel H, Mandelkow EM, Biernat J, Mandelkow E.
Novel diffusion barrier for axonal retention of Tau in neurons and its failure in neurodegeneration.
EMBO J. 2011 Oct 18;30(23):4825-37. doi: 10.1038/emboj.2011.376.
PubMed PMID: 22009197

Timm T, von Kries JP, Li X, Zempel H, Mandelkow E, Mandelkow EM.
Microtubule affinity regulating kinase activity in living neurons was examined by a genetically encoded fluorescence resonance energy transfer/fluorescence lifetime imaging-based biosensor: inhibitors with therapeutic potential.
J Biol Chem. 2011 Dec 2;286(48):41711-22. doi: 10.1074/jbc.M111.257865. Epub 2011 Oct 7.
PubMed PMID: 21984823

Zempel H, Thies E, Mandelkow E, Mandelkow EM.
Abeta oligomers cause localized Ca(2+) elevation, missorting of endogenous Tau into dendrites, Tau phosphorylation, and destruction of microtubules and spines.
J Neurosci. 2010 Sep 8;30(36):11938-50. doi: 10.1523/JNEUROSCI.2357-10.2010. Erratum in: J Neurosci. 2012 Apr 25;32(17):6052.
PubMed PMID: 20826658

Miura Y, Sakurai Y, Hayakawa M, Shimada Y, Zempel H, Sato Y, Hisanaga S, Endo T.
Translocation of lysosomal cathepsin D caused by oxidative stress or proteasome inhibition in primary cultured neurons and astrocytes. Biol Pharm Bull. 2010;33(1):22-8.
PubMed PMID: 20045930

Curriculum Vitae
Academic education
08/2018 Medical Approbation, University of Bonn & Medical thesis, magna cum laude (1,0)
2015–2018 Clinical Medicine, Student, University Bonn & Postdoc (50%), DZNE, Bonn
12/2013 PhD Thesis, Biochemistry, summa cum laude (1,0*), Hamburg University & Max-Planck Groups for Structural Molecular Biology
2006–2008 Clinical Medicine, Medical and Dental University Tokyo, Japan
2005–2006 Biophysics & Genetics, Kyoto University, Japan
2002–2006 Biochemistry & Biophysics, MSc in Biochemistry, Berlin University (FU) & Charité, Berlin, Germany
2000–2002 Abitur, with honors, top of class (grade 1,2) Gymnasium Oberasbach b. Nürnberg
1999–2000 High-School Diploma, with honors, Rancocas Valley High School, NJ, USA
Clinical course / work experience 
Since 09/2018 Principal Investigator & Medical Doctor Institute for Human Genetics, University Clinic Cologne
04/2018–08/2018 Chief Scientific Officer (Start-up company, EF incubator) MedXact technology ltd. (now Juniper Medical Computing), Berlin/London
2017–2018 Clinical Rotations: Neurology (Univ. Liège, Belgium), Surgery (Univ. Würzburg, Germany), Internal Medicine (Univ. La Laguna, Spain) 
2010–2017 PhD & PostDoc by German Center for Neurodegenerative Diseases (DZNE), Bonn Max-Planck Group for Struct. & Mol. Biology, Hamburg

Team

Nadine Allroggen, MD candidate
Sara Bachmann, M.Sc., PhD candidate
Michael Bell, M.Sc., PhD candidate
Jennifer Klimek, biological-technical assistant
Felix Langerscheidt, B.Sc. candidate
Julia Oly, B.Sc., M.Sc. candidate
Noah Tjiong, MD candidate
Jeanne-Franca Vollmar, MD candidate

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