Institute of Human Genetics

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  • WG Functional Genetics of Neurodegeneration and Neurological Diseases
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AG Functional Genetics of Neurodegeneration and Neurological Diseases

Unsolicited applications for scientific doctoral positions (m/f/d) and postdoctoral positions (m/f/d) are always welcome!

The same applies to applications for Bachelor's (B.Sc.) and Master's (M.Sc.) theses.

All applications should include an informative curriculum vitae in tabular form, a transcript of the modules completed to date or proof of previous degrees as well as a brief description of your professional aptitude and personal motivation. Further attachments are optional.

The research interest of the Functional Genetics of Neurodegeneration and Neurological Diseases group, headed by Dr. Dr. rer. nat. Hans Zempel, is to elucidate the pathomechanisms of neurodegenerative and rare genetic neurological diseases. We are working on the identification and characterization of factors that influence neuronal and synaptic function. Rare genetic diseases often provide clues to the development and treatment of age-associated diseases of a non-genetic nature - such as Alzheimer's-type dementia.

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

Our research focus is on the cellular and molecular mechanisms and therapy of

  • Dementias of the Alzheimer type and related tauopathies, e.g. frontotemporal dementias (Pick's disease, corticobasal degeneration, progressive supranuclear palsy)
  • Mitochondriopathies, such as polymerase-gamma mutations
  • Neurological diseases caused by cytoskeletal disorders, cellular transport disorders or neuronal migration defects (hereditary spastic paraplegia (HSP), lissencephalopathies)
  • 2-hydroxyglutaric aciduria and related syndromes
  • Lysosomal storage disorders
  • Neuronal cell polarity

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

Third-party funds
  • Else Kröner-Fresenius Foundation
  • Jürgen Manchot Foundation
  • Study Foundation of the German People
  • Cologne Fortune
  • German Research Foundation (DFG)
  • German Research Council (GRC)
  • Alzheimer's Research Initiative (AFI)
Selected publications

Bell-Simons M, Buchholz S, Klimek J, Zempel H.
Laser-Induced Axotomy of Human iPSC-Derived and Murine Primary Neurons Decreases Somatic Tau and AT8 Tau Phosphorylation: A Single-Cell Approach to Study Effects of Acute Axonal Damage.
Cell Mol Neurobiol. 2023 May 12. doi: 10.1007/s10571-023-01359-z.
PubMed PMID: 37171549

Tjiang N,Zempel H.
A mitochondria cluster at the proximal axon initial segment controls axodendritic TAU trafficking in rodent primary and human iPSC-derived neurons.
Cell Mol Life Sci. 2022 Feb 4;79(2):120. doi: 10.1007/s00018-022-04150-3.
PubMed PMID: 35119496

Schützmann MP*, Hasecke F*, Bachmann S*, Zielinski M, Hänsch S, Schröder GF, Zempel H#, Hoyer W.#(*indicates shared first-authorship, #indicatesshared last-authorship)
Endo-lysosomal Aβ concentration and pH trigger formation of Aβ oligomers that potently induce tau missorting.
Nat Commun. 2021 Jul 30;12(1):4634. doi: 10.1038/s41467-021-24900-4.
PubMed PMID: 34330900

Bachmann S, Bell M, Klimek J, Zempel H.
Differential Effects of the Six Human TAU Isoforms: Somatic Retention of 2N-TAU and Increased Microtubule Number Induced by 4R-TAU.
Front Neurosci. 2021 May 25;15:643115. doi: 10.3389/fnins.2021.643115.
PubMed PMID: 34113229

Bell M, Bachmann S, Klimek J, Langerscheidt F, Zempel H.
Axonal TAU Sorting Requires the C-terminus of TAU but is Independent of ANKG and TRIM46 Enrichment at the AIS.
Neuroscience. 2021 May 1;461:155-171. doi: 10.1016/j.neuroscience.2021.01.041. Epub 2021 Feb 6.
PubMed PMID: 33556457

Bachmann S, Linde J, Bell M, Spehr M, Zempel H, Zimmer-Bensch G.
DNA Methyltransferase 1 (DNMT1) Shapes Neuronal Activity of Human iPSC-Derived Glutamatergic Cortical Neurons.
Int J Mol Sci. 2021 Feb 18;22(4):2034. doi: 10.3390/ijms22042034.
PubMed PMID: 33670788

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, 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

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

Dr.--Zempel-Hans
Dr. Hans Zempel, PhD, Degree in Biochemistry

Physician

Publications (PubMed)

telephone icon+49 221 478-86612
fax icon+49 221 478-86465
Academic education
08/2018Medical Approbation, University of Bonn & Medical thesis, magna cum laude (0,5)
2015–2018Clinical Medicine, Student, University Bonn & Postdoc (50%), DZNE, Bonn
12/2013PhD Thesis, Biochemistry, summa cum laude (1,0*), Hamburg University & Max-Planck Groups for Structural Molecular Biology
2006–2008Clinical Medicine, Medical and Dental University Tokyo, Japan
2005–2006Biophysics & Genetics, Kyoto University, Japan
2002–2006Biochemistry & Biophysics, MSc in Biochemistry, Berlin University (FU) & Charité, Berlin, Germany
2000–2002Abitur, with honors, top of class (grade 1,2) Gymnasium Oberasbach b. Nürnberg
1999–2000High-School Diploma, with honors, Rancocas Valley High School, NJ, USA
Clinical course / work experience 
Since 09/2018Principal Investigator & Medical Doctor Institute for Human Genetics, University Clinic Cologne
04/2018–08/2018Chief Scientific Officer (Start-up company, EF incubator) MedXact technology ltd. (now Juniper Medical Computing), Berlin/London
2017–2018Clinical Rotations: Neurology (Univ. Liège, Belgium), Surgery (Univ. Würzburg, Germany), Internal Medicine (Univ. La Laguna, Spain) 
2010–2017PhD & PostDoc by German Center for Neurodegenerative Diseases (DZNE), Bonn & Max-Planck Group for Struct. & Mol. Biology, Hamburg
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The team

Daniel Adam, M.Sc., PhD student
Gift Adiawa, M.Sc., PhD student
David Benitez Alvarez, M.Sc., PhD student
Cagla Cakmak, M.Sc, PhD student
MhD Aghyad Al Kabbani, M.Sc, PhD student
Jennifer Klimek, Biological-technical assistant
Felix Langerscheidt, M.Sc., PhD student
Thilo Löhr, B.Sc., Master student