We reprogram cells to better understand brain function and to develop novel treatments for neurological disorders

Frank Edenhofer
Univ.-Prof. Dr.

Institute of Molecular Biology
Genomics, Stem Cell Biology and Regenerative Medicine
University of Innsbruck

Technikerstraße 25

A-6020 Innsbruck 

Degrees

PhD in Biology

Current SPIN Students

Gabriella Fenkart, Larissa Traxler

Current Research

Frank Edenhofer’s research group has a long standing interest in stem cell biology, cellular reprogramming and neural regeneration. His group analysed the core transcriptional network regulating pluripotency and neural stemness Including Oct-4, Nanog, Sox2, Brn-2 and Pax-6. Moreover, he developed biologically active recombinant cell-penetrating transcription factors to achieve cellular reprogramming into transgene-free induced pluripotent stem cells (iPSC) and their targeted neural differentiation. More recently, his group devised pioneering studies in the field of cellular reprogramming by developing a strategy to directly convert human skin-derived fibroblasts to induced neural stem cells (iNSCs). These are able to differentiate into neurons, astrocytes and oligodendrocytes in vitro and in vivo and exhibit a virtually unlimited self renewal capacity. By that the Edenhofer group were the first to demonstrate that one can artificially generate somatic stem cells that are functionally equivalent to stem cells originated from endogenous sources. iNSCs were and are being validated in various preclinical models such as myelin deficiency, Multiple Sclerosis, and Parkinson’s disease. Currently, the group focuses on i) the understanding of molecular mechanisms underlying neural transdifferentiation and ageing, ii) patient-specific iNSCs for disease modeling and cell therapy targeted at Parkinson’s Disease, Multiple Sclerosis and Vanishing White Matter Disease and iii) derivation of complex 3D neural tissue organoids to more faithfully recapitulate neural pathology in vitro. Our findings will help to develop reliable models of CNS function and dysfunction and provide a novel cellular basis for autologous cell replacement therapy.

 

Key Techniques/Methods:

- Stem cell technology: Human and mouse pluripotent stem cells, Neural stem cells; Upscaling in 3D suspension culture

- Targeted neural differentiation (2D, semi-3D, 3D)

- Mini-brain derivation

- Immunihistochemistry, histology, confocal microscopy, electron microscopy.

- Cellular reprogramming technologies comprising viral vectors (Lenti-, Retro-, Sendai-Virus), synthetic mRNA, cell-permeant proteins; Generation of transgene-free iPSCs and iNSCs

  • Genome-wide comparative genomics, gene regulatory networks and analysis of cis-regulation in vivo.
  • Recombinant protein production in bacteria, yeast, sf9 and mammalian cells; protein purification and validation; Western, EMSA, ChIP

 

Selected Publications

Kwok, C.K., Ueda, Y., Kadari, A., Günther, K., Heron, A., Schnitzler, A.C., Rook, M., Edenhofer, F. (2017) Scalable stirred suspension culture for the generation of billions of human induced pluripotent stem cells using single-use bioreactors (2017) J. Tiss. Eng. Reg. Med. in press

Appelt-Menzel,  A., Cubukova A., Günther K., Edenhofer F., Piontek J., Krause G., Stüber T., Walles H., Neuhaus W., Metzger M. (2017) Establishment of a Human Blood-Brain Barrier Co-culture Model Mimicking the Neurovascular Unit Using Induced Pluri- and Multipotent Stem Cells. Stem Cell Rep.. 2017 Mar 22. pii: S2213-6711(17)30088-7. doi: 10.1016/j.stemcr.2017.02.021. [Epub ahead of print]

Wörsdörfer P*, Bosen F, Gebhardt M, Russ N, Zimmermann K, Komla Kessie D, Sekaran T, Egert A, Ergün S, Schorle H, Pfeifer A, Edenhofer F*, Willecke K. (2017) Abrogation of Gap Junctional Communication in ES Cells Results in a Disruption of Primitive Endoderm Formation in Embryoid Bodies. Stem Cells. 2017 Apr;35(4):859-871. doi: 10.1002/stem.2545. Epub 2016 Dec 20.

*corresponding authors           

Scognamiglio et al., F. Edenhofer, P. Bertone, W. Huber, F. van der Hoeven, A. Smith and A. Trumpp. Myc Depletion Induces a Pluripotent Dormant State Mimicking Diapause, Cell 2016, 164(4): 668–680. http://doi.org/10.1016/j.cell.2015.12.033.       

Thier, M , P. Wörsdörfer, Y. B. Lakes, R. Gorris, S. Herms, T. Opitz, D. Seiferling, T. Quandel, P. Hoffmann, M. M. Nöthen, O. Brüstle & F. Edenhofer, Direct conversion of fibroblasts into tripotent neural stem cells, Cell Stem Cell 2012 10(4):473-9. Epub 2012 Mar 22. Invited paper for the ‘Falling Walls’ Conference Berlin, 2012.   

Patsch, C., M. Peitz, D.M. Otte, D. Kesseler, J. Jungverdorben, F.T. Wunderlich, O. Brustle, A. Zimmer & F. Edenhofer. Engineering cell-permeant FLP recombinase for tightly controlled inducible and reversible overexpression in embryonic stem cells. Stem Cells 28 (2010) 894-902. Selected by Faculty of 1000 Biology – Most important advances in biology.