Document 7904557

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First Annual Meeting
Pioneering the Use of Genomic Biomarkers in Assessing Risk to
Environmental and Human Health
• An established and effective collaboration
• A well-established need
• Particular local strengths:
 model systems
 high throughput approaches
 toxicology
• Strategy and goals
The Indiana University Consortium for Environmental
Genomics and Toxicology
• The Center for Genomics and Bioinformatics (IUB)
• The Center for Environmental Health (IUSOM)
• The School of Public and Environmental Affairs
• The Center for Research in Environmental Science
(IUB)
High-throughput experiments catalog all the genetic responses to drugs:
Control mRNA
RT
RT
Contro
l
Treatment
Treated mRNA
Control labeled target
Microarray response data
Treaated labeled target
•
The summary is a signature of a drug’s effects.
•
A gene expression signature of androgen
stimulation was defined from gene expression
profiles of LNCaP cells stimulated with the
synthetic androgen R1881 for 12 hr and 24 hr,
as compared to androgen-deprived LNCaP
cells.
•
The 27 gene signature contains both androgeninduced and androgen-repressed genes, shown
here by row-normalized heat map.
A Strategy:
High throughput water quality testing using gene expression signatures in Daphnia
Control mRNA
• Test stressors in the lab
• Make a catalog of
signatures
RT
RT
Contr
ol
Environmental
stress
• Use those signatures to
guide toxicological work in
mammals
• Look for those signatures to
assess water quality
Stress mRNA
Control labeled target
Gene response data
Stressed labeled
target
The Results:
• Assessment – Sensitivity and informationrich measurement of "bio-active" titers.
• Diagnosis – Enhanced understanding of
the mechanisms of toxicity and a better
assessment of risk.
The Indiana University Consortium for Environmental Genomics and Toxicology
Dr. John Colbourne
Associate Scientist
Genomics Director, CGB (IUB)
Barbara Hocevar
Assistant Professor
Department of Pharmacology and
Toxicology
School of Medicine (IUPUI)
Peter Cherbas
Professor Biology
Director, CGB (IUB)
James Klaunig
Robert B. Forney Professor
Dept. of Pharmacology and Toxicology
Director, Center for Environmental
Health
School of Medicine (IUPUI)
Lisa Kamendulis
Assistant Professor
Department of Pharmacology and
Toxicology
School of Medicine (IUPUI)
Keith Clay
Professor of Biology
Director, IU Research and Teaching
Preserve
Director, CRES (IUB)
Joseph Shaw
Assistant Professor
School of Public and Environmental
Affairs (IUB)
First Annual Meeting