Our group focuses on pharmacological and toxicological research in the areas of neurodevelopment and neurodegeneration. New cell models and endpoints are being established and used to obtain information relevant for human health and safety without animal experiments (Fig. I).
One research line (Fig. II) addresses the question on how toxicants affect very early fetal development of the nervous system. We use pluripotent stem cells that are first differentiated to neural precursors and then further to glial cells or neurons. Using these models of “tissue generation in a cell culture dish”, we examine epigenetic alterations of the cells and how they are affected by toxicants. Moreover, we follow a systems toxicology approach by using gene expression profiling and other techniques that yield rich information on many endpoints, in order to define toxicity signatures of different classes of chemicals and signaling molecules.
A second research line (Fig. III) is involved with key mechanisms of neurodegenerative diseases and their modeling in cell cultures of human neurons or in co-cultures of neurons and glial cells. Four major pathological events are observed in many disease, including Alzheimer’s disease (AD) and Parkinson’s disease (PD): protein aggregation, inflammation, oxidative stress and mitochondrial dysfunction. We are interested in their modulation by drugs, in high content screening of cellular alterations and in the chemical biology involved in protein modifications.
Besides experimental research, we also conceptualize new toxicological approaches within the transatlantic think tank for toxicology (t4), and we are strongly involved in promoting research and development in the field of alternative methods to animal experimentation, within our joint venture of CAAT-Europe in Konstanz and CAAT at the Bloomberg School of Public Health at Johns-Hopkins University in Baltimore.
Overview on the role of the chair and its topic
Overview on in vitro methods to replace animal experiments and on the 3R principle
- A Framework Program for the Teaching of Alternative Methods (Replacement, Reduction, Refinement) to Animal Experimentation
Overview on stem cell ethics
- The Biological and Ethical Basis of the Use of Human Embryonic Stem Cells for In Vitro Test Systems or Cell Therapy
Overview on assay development