- Animal testing and alternatives
- Anesthesia and Neurotoxicity Research
- Pluripotent Stem Cells Research
- MicroRNA in disease regulation
- Viral Infectious Diseases and Gene Expression in Insects
- Pesticide Exposure and Toxicity
- Computational Drug Discovery Methods
- Environmental Toxicology and Ecotoxicology
- Circular RNAs in diseases
- Neurogenesis and neuroplasticity mechanisms
- Cancer-related molecular mechanisms research
- Genetic Neurodegenerative Diseases
- Hedgehog Signaling Pathway Studies
- Pharmacological Effects and Toxicity Studies
- 3D Printing in Biomedical Research
- Heavy Metal Exposure and Toxicity
- Graphene and Nanomaterials Applications
- Carcinogens and Genotoxicity Assessment
- Reproductive System and Pregnancy
- Nerve injury and regeneration
- Cytokine Signaling Pathways and Interactions
- Congenital gastrointestinal and neural anomalies
- Renal and related cancers
- Health, Environment, Cognitive Aging
- Bone Tissue Engineering Materials
University of Konstanz
2014-2025
Humane Society of the United States
2025
Austrian Institute of Technology
2024
Biobyte Solutions (Germany)
2022
Centre for Human Drug Research
2022
Joint Research Centre
2013-2014
In many industrial sectors, there is a need for reliable ways to evaluate the safety of chemicals with methods anchored human biology and pathology. For this purpose, animal-free new approach (NAMs) have been developed implemented in various stages risk assessment. Now it time assemble individual NAMs into comprehensive next-generation assessment (NGRA) strategy. The European Horizon 2020 RISK-HUNT3R project (Risk integrating human-centric testing strategies promoting 3Rs) has designed...
In the European regulatory context, rodent in vivo studies are predominant source of neurotoxicity information. Although they form a cornerstone neurotoxicological assessments, costly and topic ethical debate. While public expects chemicals products to be safe for developing mature nervous systems, considerable numbers commerce have not, or only limited extent, been assessed their potential cause neurotoxicity. As such, there is societal push toward replacement animal models with vitro...
On occasion of the DNT5 meeting in Konstanz, Germany (April-2024), participants brainstormed on future challenges concerning a regulatory implementation developmental neurotoxicity (DNT) vitro test battery (DNT-IVB). The five discussion topics below outline some key issues, opportunities and research directions for next several years: (1) How to contextualize DNT hazard with information potential maternal toxicity or other domains (non-DNT)? Several approaches how use cytotoxicity data from...
The regular workshops held by the Center for Alternatives to Animal Testing (CAAT) on biology-inspired microphysiological systems (MPS) taking place every four years, have become a reliable measure assess fundamental scientific, industrial and regulatory trends translational science in MPS-field from bird's eye view. 2023 workshop participants at that time concluded technology as used within academia has matured significantly, underlined broad use of MPS steadily increasing number high...
Developmental toxicity in vitro assays have hitherto been established as stand-alone systems, based on a limited number of toxicants. Within the embryonic stem cell-based novel alternative tests project, we developed test battery framework that allows inclusion any developmental assay and explores responses such systems to wide range drug-like compounds. We selected 28 compounds, including several biologics (e.g., erythropoietin), classical pharmaceuticals roflumilast) also six environmental...
Hazard assessment, based on new approach methods (NAM), requires the use of batteries assays, where individual tests may be contributed by different laboratories. A unified strategy for such collaborative testing is presented. It details all procedures required to allow test information usable integrated hazard strategic project decisions and/or regulatory purposes. The EU-ToxRisk developed a provide regulatorily valid data, and exemplified this using panel > 20 assays (with 50 endpoints),...
Public awareness and discussion about animal experiments replacement methods has greatly increased in recent years. The term 'the Three Rs', which stands for the Replacement, Reduction Refinement of experiments, is inseparably linked this context. A common goal within Rs scientific community to develop predictive non-animal models better integrate all available data from vitro, silico omics technologies into regulatory decision-making processes regarding, example, toxicity chemicals, drugs...
The in vitro test battery of the European research consortium ESNATS ('novel stem cell-based systems') has been used to screen for potential human developmental toxicants. As part this effort, migration neural crest (MINC) assay evaluate chemical effects on function. It identified some drug-like compounds addition known environmental hits included HSP90 inhibitor geldanamycin, chemotherapeutic arsenic trioxide, flame-retardant PBDE-99, pesticide triadimefon and histone deacetylase inhibitors...
Abstract The major advantage of the neuronal cell culture models derived from human stem cells is their ability to replicate crucial stages neurodevelopment such as commitment lineage and subsequent differentiation into glial‐like cell. In these studies we used mixed neuronal/glial NTERA‐2 (NT‐2) line, which has been established pluripotent testicular embryonal carcinoma cells. After characterization different neuronal‐ phenotype toxicity were performed evaluate whether this model would be...
Banning or reduction of the use animals for laboratory experiments is a frequently-discussed societal and scientific issue. Moreover, usefulness needs to be considered in any decision process on permission specific animal studies. This complex issue often simplified generalized media around question, "Are useful as model?" To render an emotional discussion about experimentation more rational, it important define "usefulness" structured transparent way. achieve such goal, many sub-questions...
Identification of neurotoxic drugs and environmental chemicals is an important challenge. However, only few tools to address this topic are available. The aim study was develop a neurotoxicity/developmental neurotoxicity (DNT) test system, using the pluripotent mouse embryonic stem cell line CGR8 (ESCs). system uses ESCs at two differentiation stages: undifferentiated ESC-derived neurons. Under each condition, concentration–response curves were obtained for three parameters: activity tubulin...
Human cell-based toxicological assays have been used successfully to detect known toxicants, and distinguish them from negative controls. However, there is at present little experience on how deal with hits screens of compounds yet unknown hazard. As a case study this issue, we characterized human interferon-beta (IFNβ) as potential developmental toxicant affecting neural crest cells (NCC). The protein was identified hit during screen clinically drugs in the 'migration inhibition crest'...
Cell-based test methods with a phenotypic readout are frequently used for toxicity screening. However, guidance on how to validate the hits and integrate this information other data purposes of risk assessment is missing. We present here such procedure exemplify it case study neural crest cell (NCC)-based developmental picoxystrobin. A library potential environmental toxicants was screened in UKN2 assay, which simultaneously measures migration cytotoxicity NCC. Several strobilurin...
MicroRNAs (miRNAs) are implicated in the epigenetic regulation of several brain developmental processes, such as neurogenesis, neuronal differentiation, neurite outgrowth, and synaptic plasticity. The main aim this study was to evaluate whether miRNA expression profiling could be a useful approach detect vitro neurotoxicity. For purpose, we assessed changes caused by methyl mercury chloride (MeHgCl), well-known neurotoxicant, comparing carcinoma pluripotent stem cells (NT-2) with human...