Our laboratory focuses on using zebrafish (Danio rerio) as systems toxicology model. There are many dimensions to our research program, but all are centrally focused on exploiting the unique advantages of zebrafish to protect and improve human and environmental health. Our central dogma is that the bioactivity of chemicals and nanomaterials are strictly governed by their inherent structures, and these structures permit interactions with biological systems to alter biological activity. Thus, we want to help the field eventually predict the biocompatibility of the chemical universe. We largely use early life stage zebrafish for our research because early developmental processes are well conserved across species and the transparent embryos develop externally which greatly facilitates evaluations. Additionally, nearly the entire genetic code is expressed and active during early life stages, so nearly all potential targets for test chemicals are present. Therefore, the dynamic zebrafish embryo serves as the ultimate biological sensor for external chemicals. This allows us to use chemical and nanomaterial structural information, coupled with the biological responses they produce in zebrafish, as anchors for mechanistic and structure response relationship research. We also use these general approaches to help guide the development of safer (green) chemicals and nanomaterials. Over the past several years we have developed automated high throughput instrumentation to accelerate phenotype discovery and we have evaluated the bioactivity of thousands of chemicals and mixtures including, polycyclic aromatic hydrocarbons (PAHs), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), ethanol, flame retardants, nicotine, pesticides, pharmaceuticals, and complex environmental mixtures. We employ numerous systems and bioinformatic approaches to pursue toxicity mechanisms with a substantial effort focused on genetics, transcriptomic, small non coding RNAs, metabolomics, and pathway analysis. Finally, we have studies in the area of tissue regeneration. We are specifically developing new methods and approaches to discover the molecular pathways that prevent or promote vertebrate tissue regeneration with the goal to translate zebrafish discoveries to the clinic.