51st Annual Meeting & ToxExpo - Society of Toxicology

Society of Toxicology 2012
Scientific
Symposia
Characterizing Toxic Modes of Action
and Pathways to Toxicity
Realizing the Vision of 21st Century Toxicity
Testing: Genetic Approaches to Pathway Analysis
Thursday, March 15, 9:00 AM to 11:45 AM
Chairperson(s): Chris Corton, US EPA, Research Triangle Park, NC,
and Lyle Burgoon, US EPA, Durham, NC.
Sponsor:
Molecular Biology Specialty Section
Endorsed by:
In Vitro and Alternative Methods Specialty Section
Mechanisms Specialty Section
The US National Academy of Science (NAS) report, “Toxicity Testing
in the 21st Century,” outlined a vision that virtually all routine
toxicity testing would be conducted in human cell lines by evaluating
cellular responses of toxicity pathway assays using high-throughput
tests. Dose-response modeling of perturbations of pathway function
would be organized around computational systems biology models of
the circuitry underlying each toxicity pathway. Although there is a
growing consensus that this vision will one day become reality, the
difficult task of linking changes in the expression or modification of
components in pathways to toxicity have yet to be fully realized. There
is a clear need to better incorporate new and existing genetic tools that
can be routinely used by toxicologists allowing relationships between
chemical exposure, genetic networks, and phenotypic responses to be
better understood. This symposium brings together experts to discuss
genetic analysis of pathways that can be generally applied to toxicology
and as such will help move us toward realizing the vision of the NAS
report. This important topic will begin with a discussion on global
approaches to discover genetic targets of disease, drugs, and environmental
chemicals by coupling transcript profiling with GWAS.
To expand on this information, widely applicable high-throughput
approaches to identify gene, pathway, and phenotypic relationships
using small inhibitor RNA arrays will be addressed. Final discussions
will discuss genetic approaches in vertebrates to discover biomarkers
of pathways and gene-chemical interactions applicable to predicting
mode of action of cancer and developmental toxicity. The summary
provided will bring together the salient findings in the previous talks
to highlight bioinformatic NextGen risk assessment approaches that
can assist the toxicologist to enable linkages of chemicals, genes/
pathways, and diseases in chemical risk assessment. This topic will
appeal to a wide audience interested in the promising approaches for
the analysis and use of pathway perturbations in toxicity testing.
• A Reverse Engineering Approach to Constructing Networks of
Chemical Response. Eric Schadt, Pacific Biosciences, Menlo Park,
CA.
The Thematic Track information can be found on pages 8–9.
• Expanding the Scope of Loss of Function Genomic Screening
with RNAi Cell Microarrays. Juha Rantala, Oregon Health and
Science University, Corvallis, OR.
• Use of Predictive Markers of Cancer Mode of Action through
Integration of Genetics and Genomics. Chris Corton, US EPA,
Research Triangle Park, NC.
• Rapid In Vivo Assessment of Chemical-Gene Interactions in
Embryonic Zebrafish. Robert Tanguay, Oregon State University,
Corvallis, OR.
• Mashing the Diseaseome, Toxicogenomics, and Frozen Pizzas:
Network Systems Biology and Its Impacts on NexGen Risk
Assessments. Lyle Burgoon, US EPA, Durham, NC.
Thematic Session
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SOT’s 51 st Annual Meeting