Center Research Highlights

We are designing 3-D organotypic culture models for the Lung, Kidney, Liver and Testis using initial technologies from UW funded projects (Nanotoxicology Center, Center for Nanotechnology and our UH2 grant from the National Institutes of Health for microphisiological systems). Two of our systems (kidney and liver) build upon established microfluidic culture approaches. For the lung, we designed an air-liquid interface culture system using differentiated primary tracheal epithelial cells. For the testis, we designed a co-culture system that has been proven to mimic testicular morphogenesis and function in vitro for over two weeks. Our Center includes plans for incorporating technological innovations such as cell-specific tagging (Ribotag) of transcriptomic responses and microfluidic applications that are developed in one organotypic culture and then transferred to our other organ systems as validation and lessons learned evolve.

Our cultures use common markers of response at multiple levels of biological evaluation (molecular to cell and tissue level) to facilitate comparisons of culture responses to metals and engineered nanomaterials (ENMs) across organs and to inform our mechanistic understanding of how these compounds work using adverse outcome pathway (AOP) models. Our Project 5 is designing a systems-based approach for evaluating and testing AOP based hypotheses across Center organotypic cultures, dose, and type of metal-based ENM. Our AOP hypotheses includes evaluation of oxidative and inflammatory pathways, windows of susceptibility, and genetic evaluations of ENM responses after both acute and 14 day exposures within a toxicokinetic and dynamically driven risk assessment framework.