Microscopy and Flow Cytometry
• Confocal, laser-microdissection
• BD FACSCanto II HTS
• Guava PC
• Bio-Plex protein array system
• FCS Express 4.0
Necropsy and Histopathology
• Routine and perfusion fixation
• Routine and specialized tissue sectioning
• Assay development and validation services
Transgenic Rodent Facility
• Specialized breeding and management of rodent colonies
Human Health Risk Assessment
• PB/PK and PB/PD modeling
• Tissue response modeling
• Systems biology approach
Fit for purpose in vitro assays
To move toward the reduction and/or replacement of animal models, we continue to develop fit-for-purpose in vitro assays that examine cellular pathway responses in models that accurately reflect the relevant biology of the in vivo system where effects occur. Defining the system and ensuring biological relevance of the assay begins with choosing the appropriate model, determining whether the model contains all of the relevant biology, and testing various cellular outputs using positive and negative control compounds to ensure that the system can recapitulate the endpoint of interest (gene/protein induction, proliferation, cell cycle arrest, apoptosis, etc.). Assays that have been vetted in this way can be used with confidence to probe the signaling network and test for chemical induced perturbations.
The Hamner approach to developing fit-for-purpose in vitro assays that are useful for evaluating the key events in a toxicity pathway and performing dose-response assessments sufficient for defining regions of safety for chemical exposure. At the Hamner our faculty have extensive experience in the development and evaluation of in vitro assays for key signaling events and cellular outcomes for many toxicological endpoints: including PPARα induction of proliferation in hepatocytes, estrogen receptor-mediated proliferation in human uterine cells, inhibition of steroidogenesis in Leydig cells, genotoxicity and DNA damage response, oxidative stress response and cellular damage, differentiation of adipocyte progenitor cells.
Gene Expression Microarrays
We have over 15 years of experience advancing the application of microarrays for toxicology studies. This technology has been used to determine benchmark dose but to determine affected pathways as defined by Gene Ontology, Reactome, GeneGo, etc. This approach has contributed to tiered approaches to risk assessments and rank order categorization.
In addition to gene expression data, we use ChIP-seq data streams and untargeted metabolomics to study modes-of-action. Due to the dense nature of high-throughput biological data, we place special emphasis on data visualization and interactive tools.