Stem cells models for studies of neurodegenerative diseases – University of Copenhagen

Stem cells models for studies of neurodegenerative diseases

Our research activities are focused on disease modelling using induced pluripotent stem cells (iPSC) from patients and their CRISPR-Cas9 gene edited controls. Besides neural cell type specific pathologies I am keen on understanding overlapping dysfunctions amongst different types of dementia. I believe that comprehensive understanding of such molecular
commonalities may provide opportunities for novel interventions that are beneficial for an array of related diseases facilitating cost effective drug development.

Current projects

We are currently working with Frontotemporal dementia (FTD) and Alzheimer’s disease (AD). Here we differentiate our cellular models into neurons, astrocytes and microglia and assess cellular phenotypes compared to their isogenic controls.

BrainStem and NeuroStem (Innovation Foundation Denmark) support the disease in the dish modeling of both FTD and AD.

We are also evaluating the dog as a model for AD research and compare iPSC derived neurons from dogs with canine cognitive deficits (CCD) to the human AD iPSC derived neurons (funded by the Dansk Forskningsråd).

Publications

  • Zhang, Y., Schmid, B., Nikolaisen, N.K., Rasmussen, M.A., Aldana, B.I., Agger, M., Calloe, K., Stummann, T.C., Larsen, H.M., Nielsen, T.T., Huang, J., Xu, F., Liu, X., Bolund, L., Meyer, M., Bak, L.K., Waagepetersen, H.S., Luo, Y., Nielsen, J.E., Consortium, F.R., Holst, B., Clausen, C., Hyttel, P., Freude, K.K., (2017) Patient iPSC-Derived Neurons for Disease Modeling of Frontotemporal Dementia with Mutation in CHMP2B. Stem Cell Reports 8, 648-658.
  • Aldana, B.I., Zhang, Y., Lihme, M.F., Bak, L.K., Nielsen, J.E., Holst, B., Hyttel, P., Freude, K.K., Waagepetersen, H.S., (2017) Characterization of energy and neurotransmitter metabolism in cortical glutamatergic neurons derived from human induced pluripotent stem cells: A novel approach to study metabolism in human neurons. Neurochem Int
  • Zhou, S., Ochalek, A., Szczesna, K., Avci, H.X., Kobolak, J., Varga, E., Rasmussen, M., Holst, B., Cirera, S., Hyttel, P., Freude, K.K., Dinnyes, A., (2016a) The positional identity of iPSC-derived neural progenitor cells along the anterior-posterior axis is controlled in a dosage-dependent manner by bFGF and EGF. Differentiation 92, 183-194.
  • Freude, K.K., Penjwini, M., Davis, J.L., LaFerla, F.M., Blurton-Jones, M., (2011) Soluble amyloid precursor protein induces rapid neural differentiation of human embryonic stem cells. J Biol Chem 286, 24264-24274.
  • Kalscheuer, V.M., Freude, K., Musante, L., Jensen, L.R., Yntema, H.G., Gecz, J., Sefiani, A., Hoffmann, K., Moser, B., Haas, S., Gurok, U., Haesler, S., Aranda, B., Nshedjan, A., Tzschach, A., Hartmann, N., Roloff, T.C., Shoichet, S., Hagens, O., Tao, J., Van Bokhoven, H., Turner, G., Chelly, J., Moraine, C., Fryns, J.P., Nuber, U., Hoeltzenbein, M., Scharff, C., Scherthan, H., Lenzner, S., Hamel, B.C., Schweiger, S., Ropers, H.H., (2003) Mutations in the polyglutamine binding protein 1 gene cause X-linked mental retardation. Nat Genet 35, 313-315.