Research Groups

Portrait Andreas Hermann

Andreas Hermann

How human neurons get sick: Disease modeling of neurodegenerative diseases using hIPSCs

Previous and Current Research

Previous studies

Our initial studies were on characterization of different adult neural stem cell types from murine and human brain and human bone marrow. Special impetus was put on the regenerative capacity of the adult midbrain. We systematically characterized these populations trying to study their potential use in vivo. We then moved on characterizing induced systems including induced pluripotent stem cells and induced neural stem cells and their potential for future therapeutical use.

Current work

For three years now we have been working on human cell models of rare neurodegenerative diseases with special emphasis on neuroacanthocytosis, neuronal ceroid lipofuscinosis as well as motor neuron degeneration (using iPS cells). The overall goal is to use hiPSCs as model cells for studies on the molecular pathophysiology of rare neurodegenerative diseases. We thereby want to understand the underlying mechanisms to develop new therapeutic targets (including new concepts of targets).

We have many fully characterized hIPSCs in hand which show clear sings of neuropathology (see publications). We additionally established differentiation protocols for all neuronal cell types of interest. This enables us now to in depth analyse pathophysiological changes. We have isogenic lines and hiPSCs with tagged endogenous proteins in hand.

Goals

Overall goal: The overall goal is to understand the interaction of cell organelles, neuronal excitability and the cytoskeleton in inducing neurodegenerative events. This is of great importance since the overall question in neurodegenerative diseases is about the initial event, the diagnosis and treatment in stages prior to induction of an irreversible change.

Experimental approach: To use patient-specific induce pluripotent cell models from a (i) storage disease (NCL), (ii) aggregate prone disease (ALS) and (iii) a disease with no aggregates but hyperexcitability (ChAc) combined with state of the art live cell imaging techniques, electrophysiology and biophysical tools (PIV, laser ablation for cortex tension measurements, AFM). We will differentially characterize organelle structure and motility, excitability, cell and axonal growth and cell cortical plasticity in the different diseases. Subsequently, we will interfere with each part of the trinity and measure the consequence on the two other domains to finally understand their interactions.

Significance: The results will contribute to the understanding of the interaction of cellular structure, cellular organelle and cellular function and how this lead to neurodegeneration to provide novel drug targets for causative therapies.

Andreas Hermann Research: Figure
Shown are differentiated motor neurons derived from human iPSC which were cultivated in a microfluidic chamber to get linearized axon. By this we are able to live cell monitor organelle movement.
Andreas Hermann research: movie Legend: Live cell imaging mitochondria (red colour, using mitotracker) and lysosomes (green colour, using lysotracker) in linearized motor neurons.
Future Projects and Goals

Aim 1: Differentially analysing cell organelle, neuron excitability and cytoskeleton in three paradigmatic neurodegenerative diseases

Aim 2: Exploring the interaction of cell organelle, neuron excitability and cytoskeleton on inducing neurodegenerative events (trinity of neurodegenerative diseases)

Aim 3: We are specifically interested how defects of nuclear proteins cause axonal phenotypes using live cell imaging techniques, inhibitor studies, laser irradiation, -omics approaches.

Methodological and Technical Expertise
  • human induced pluripotent stem cells (hiPSC)
  • neuronal differentiation
  • live cell imaging
  • tagging of endogenous proteins
  • disease modeling and drug discovery
Selected Publications

Japtok J, Lojewksi X, Naumann M, Klingenstein M, Reinhardt P, Sterneckert J, Putz S, Demestre M, Boeckers TM, Ludolph AC, Liebau S, Storch A, Hermann A.
Stepwise acquirement of hallmark neuropathology in FUS-ALS iPSC models depends on mutation type and neuronal aging.
Neurobiol Dis. 2015 Aug 4. pii: S0969-9961(15)30021-8. doi: 10.1016/j.nbd.2015.07.017.

Waechter N, Storch A, Hermann A.
Human TDP43 and FUS selectively affect motor neuron maturation and survival in a murine cell model of ALS by non-cell autonomous mechanisms.
Amyotroph Lateral Scler Frontotemporal Degener 2015 Jul 15:1–11

Lojewski X, Staropoli JF, Biswas-Legrand S, Simas AM, Haliw L, Selig MK, Coppel SH, Goss KA, Petcherski A, Chandrachud U, Sheridan SD, Lucente D, Sims KB, Gusella JF, Sondhi D, Crystal RG, Reinhardt P, Sterneckert J, Schöler H, Haggarty SJ, Storch A, Hermann A*, Cotman SL*.
Human iPSC models of neuronal ceroid lipofuscinosis capture distinct effects of TPP1 and CLN3 mutations on the endocytic pathway.
Hum Mol Genet. 2014 Apr 15;23(8):2005–22. *contributed equally

Han DW, Tapia N, Hermann A, Hemmer K, Höing S, Araúzo-Bravo MJ, Zaehres H, Wu G, Frank S, Moritz S, Greber B, Yang JH, Lee HT, Schwamborn JC, Storch A, Schöler HR
Direct reprogramming of fibroblasts into neural stem cells by defined factors
Cell Stem Cells, 2012 Apr 6;10(4):465–72 (2012)

Löhle M, Hermann A, Glaß H, Kempe H, Schwarz SC, Kim JB, Poulet C, Ravens U, Schwarz J, Schöler HR, Storch A
Differentiation efficiency of induced pluripotent stem cells depends on the number of reprogramming factors
Stem Cells 30: 570–579 (2012)

CV

Since 2013
Senior neurologist and Principle Investigator Motor Neuron/FTLD degeneration group, Department of Neurology, University Clinics, TU Dresden

2005–2013
Residency in the Department of Neurology, University Clinics, TU Dresden

2005–2010
Postdoctoral Research in Experimental Neurology, TU Dresden

2001–2005
MD-PhD-student Graduate College 460 “Diagnostic and therapeutic concepts in molecular medicine”, University Ulm, Germany and University Clinics, TU Dresden

1999–2005
Medical School, University Ulm and TU Dresden, Germany

Contact

Dresden University of Technology
Division for Neurodegenerative Diseases
Fetscherstraße 74
01307 Dresden

www.als-dd.de
www.emina2.de

Intranet