Institute of Toxicology (TOXI)
The Institute of Toxicology aims to elucidate the effect of chemical substances on biological systems in the development and progression of complex diseases. Experimental approaches include understanding the modes and mechanisms of action of selected small molecules. Critical components in the cellular response pathways are identified that determine specificity and selectivity of toxic effects or disclose potential opportunities for therapeutic interventions by small molecules. The search for such novel molecules is pursued. The results of our work contribute to the improvement of strategies for avoiding health risks, the identification of novel biologically active compounds, and the development of therapeutic approaches. This general theme is implemented in the following specific topics (PIs in parentheses):
- Histone deacetylases: Understanding physiological and pathophysiological functions of individual HDACs in cancer, metabolic regulation and CNS; development of isoenzyme selective inhibitors (M. Göttlicher)
- Proteomic responses to small molecules: Focus on HDAC inhibitors and dioxins (U. Andrae until 2013)
- Mitochondrial responses to toxic insults: Analysis of cell type and organ specific mechanisms controlling mitochondrial permeability in response to chemical and oxidative impacts (H. Zischka)
- Regulatory networks controlling NF-κB activity: Understanding signal integration upstream of NF-κB in the context of inflammation, autoimmunity and cancer; identification of targets for intervention and small molecule modulators (Department cellular signal integration, D. Krappmann)
- Genetic analysis of signal processing in the immune system: Identification of critical components of signal processing in the immune system and cancer development by systematic analysis of human disease related mutations in targeted mouse models (Cooperation group with Technische Universität München: Signal processing in the immune system, A. Gewies and J. Ruland)
- Rationale for risk assessment of high production volume chemicals: Development of toxicokinetic models for target dose assessment in an integrated human/rodent and in vivo/in vitro approach; toxicodynamic analysis of the role of chemically induced antioxidant depletion (J. Filser)
- Nanoparticle toxicity: Identification and understanding of responses of the heart to the exposure toward nano-sized particles of different size and chemical composition (A. Stampfl)
- Neurotoxic peptides as selective modulators of ion channel signaling: Development of specific peptides for selective modulation of ion channels (e.g. in immune cells) starting from neurotoxic peptides of snails (conidae) or scorpions. (Junior Research Group until 2011, A. Klostermann)
- Assay Development and Screening Platform: Development of assays suitable for high throughput screening of small molecule libraries for targets identified by HMGU research (K. Hadian, Platform established 2010)