Preclinical Research

Adequate and authentic human model systems have been lacking for the study of diseases affecting one or more organs. Human induced pluripotent stem cells (iPSCs) overcome these limitations and represent an ideal human disease model by recapitulating disease phenotypes in the culture dish.  

Our group is developing a unique and powerful platform of iPSC disease and reporter models enabling to investigate underlying pathological mechanisms and to screen and test compounds and toxins. Our experienced team combines more than 10 years of expertise in iPSC disease modeling as well as long-standing and extensive knowledge in genome editing.

Offering

• Customized generation and quality control of human iPSCs from patient samples and healthy donors.
• Genome editing in iPSCs to generate isogenic control and disease models as well as iPSC reporter cell lines.
• Use of established iPSC models from large national and international iPSC repositories.
• Robust differentiation of human iPSCs into disease-relevant cell types and tissues of (neuro)ectodermal, mesodermal, and endodermal origin in 2D and 3D formats.
• Multiparametric molecular and cellular phenotyping of iPSC disease models including optimization for high-content imaging.
• Continuous development, optimization, and process automation of cell-based assays.
• Compound screening, drug repurposing and evaluation of the efficacy and toxicity of drug candidates.
• Screening of novel compound candidates, approved drugs for repurposing, and potentially toxic substances to assess efficacy, toxicity, and disease-relevant mechanisms of action.
• Functional characterization of complex iPSC-based models, including brain organoids and engineered cardiac muscle tissues.

The preclinical research group develops new therapeutic approaches for neurological, in particular neurodegenerative diseases of childhood. This group of diseases primarily includes rare diseases with no existing therapies but a great need for therapy. Therapeutic approaches are developed by identifying useful intracellular targets that can be specifically influenced by drugs in order to reverse the pathophysiology. In addition to the identification of specific targets, high-throughput drug screening methods are also used to identify untargeted therapeutically effective substances. For this purpose, new analytical methods and assays are being developed to measure a meaningful therapeutic response in vitro. Findings from these approaches can also be transferred to other neurodegenerative diseases in adulthood, as they often involve similar intracellular pathomechanisms.