iPS cell based disease modeling
Head of the Group
Dr. Ralf Kühn
Tel. +49 30 9406 3321
Fax. +49 30 9406 3327
iPS Cell-based Disease Modeling
We are using induced pluripotent stem cell (iPSC) lines to study disease mechanisms in human cells by reverse genetics. IPS cell lines can be derived by reprogramming of e.g. skin fibroblasts from healthy or diseased individuals by the expression of the four transcription factors Oct4, Sox2, Klf2 and c-Myc. Once established, iPSCs represent self-renewing cell lines at early embryonic stage which can be indefinitely propagated in vitro. Using designer nuclease technologies (TALEN, CRISPR/Cas9) it is now possible to introduce (or to correct) mutations in one or more disease related genes. These modified cells are then converted by expression of lineage-specific transcription factors into cells of interest such as dopaminergic neurons and analysed for pathologic cellular phenotypes (e.g. mitochondrial function, protein aggregation, dendrite length) with disease relevance. In addition, the cultures can be subjected to environmental manipulation (e.g. oxidative stress, toxins) or aged by interference with DNA repair pathways. By the correlation of genotypes, envirotypes and phenotypes this iPSC based analysis platform delivers new insights into human genetics, cellular biology and disease mechanisms.