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.

Many rare neurometabolic and neurodegenerative diseases of childhood still lack disease-modifying therapies despite a high unmet medical need. AG Schlotawa investigates these disorders using disease-relevant cellular models to uncover intracellular pathomechanisms, with a particular focus on lysosomal dysfunction and related biochemical changes.

The group combines patient-derived and genome-edited cell models with microscopy-based, biochemical, molecular, and omics-based analyses to identify disease-related phenotypes and pharmacologically modifiable targets. These approaches support the development of robust cellular and biochemical assays that measure therapeutic responses in vitro and provide the basis for high-throughput screening and drug repurposing strategies to identify compounds with therapeutic potential.

Since lysosomal dysfunction, impaired organelle homeostasis, and altered intracellular signaling are shared features of many neurodegenerative disorders, findings from these approaches may also be relevant to adult-onset neurodegenerative diseases.

Our expertise includes:

• Generation and characterization of cellular models for rare neurometabolic and neurodegenerative diseases.
• Investigation of primary patient-derived cells and disease-relevant cellular models using multiparametric molecular, biochemical, and microscopy-based phenotyping.
• Analysis of intracellular pathways, organelle alterations, and disease-relevant biochemical mechanisms.
• Development and optimization of disease-relevant cellular and biochemical assays for therapeutic screening.
• High-throughput drug screening to identify therapeutically active substances.