The FHCRC/UW Toxicogenomics Consortium

Project Details

Description

DESCRIPTION (provided by applicant)
A central tenet of toxicology is that with the possible exception of acute
cell necrosis, every toxic exposure leads to an alteration in the pattern of
gene expression. This altered pattern of gene expression reflects the cell?s
attempt to cope with the toxic insult, and can range from induction of
xenobiotic metabolism to the extreme of cell suicide or apoptosis. While
numerous studies have looked at changes in the expression of a limited number
of genes thought to play a role in these adaptive responses, the power of
array technology is the ability to obtain a comprehensive survey of thousands
of genes simultaneously. This global analysis of gene expression affords
researchers the ability to discern specific patterns or signatures of
expression that are associated with particular classes of toxicants. These
signatures are likely to include classes of genes not previously implicated in
response to specific toxic insult. As such the applications of array
technologies to toxicology will undoubtedly enhance our understanding of the
cellular response to toxicants, which should by inference also provide insight
into the mechanism of drug responses, toxicity, development effects and
induction of disease. The unifying theme of the present proposal is that the
comparison of gene expression profiles induced by stressors or toxicants in
cells that are differentially sensitive to their effects will be particularly
useful in dissecting the biochemical pathways underlying a toxic response.
The investigators have assembled a team experts in the areas of
biotransformations, neurodevelopmental toxicology, and carcinogenesis with the
common goal of using DNA microarray technologies to compare gene expression
profiles among mouse and rat, and human cells that are differentially
sensitive to a variety of environmental agents. A series of four projects and
a Toxicology Research Core Project, all of which make use of genetically
defined rats or mice, transgenic and knockout mice and primary human and
rodent cell cultures are proposed. The projects will be supported by an
Administrative Core and essential three facility cores. The DNA Microarray
Facility Core will provide project researchers access to the state-of-the-art
facility established at the Fred Hutchinson Cancer Research Center by
Dr. Zarbl. The Tissue Acquisition Core will project researchers access the
Transgenic/Knockout Mice facility at the University of Washington, providing
researchers access to genetically defined mice and their tissues. Recognizing
the need to look at individual cell types comprising organs, the investigators
also included within this Core access to cell enrichment technologies. The
Tissue Acquisition Core will provide researchers access to high speed cell
sorting and laser capture microdissection capabilities. The final facilities
core will provide bioinformatic and biostatistics support to the project
researchers. These latter will be required for coordinating the acquisition,
processing, storing and analyzing the large volumes of data that will be
generated by the project researchers. Each of the Cores will also interact
with other Consortium members and the central contractor through the
Toxicology Research Core Project to perform cross species and cross platform
comparisons and to develop standards for data standardization. The latter
will be essential for the generation of a public database for data generated
by all members of the Consortium.
StatusFinished
Effective start/end date9/30/017/31/08

Funding

  • National Institutes of Health: $798,244.00
  • National Institutes of Health: $1,273,217.00
  • National Institutes of Health: $1,485,707.00
  • National Institutes of Health: $1,126,959.00
  • National Institutes of Health: $765,330.00
  • National Institutes of Health: $39,500.00
  • National Institutes of Health: $1,431,019.00

ASJC

  • Environmental Science(all)
  • Medicine(all)

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