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

Treaated labeled target

Control labeled target

RT

Treated mRNA

RT

Control mRNA

Control

Treatment

Microarray response data

High-throughput experiments catalog all the genetic responses to drugs:

• 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 androgen-induced and androgen-repressed genes, shown here by row-normalized heat map.

A Strategy:

High throughput water quality testing using gene expression signatures in Daphnia

Stressed labeled target

Control labeled target

RT

Stress mRNA

RT

Control mRNA

Control

Environmental stress

Gene response data

• Test stressors in the lab

• Make a catalog of signatures

• Use those signatures to guide toxicological work in mammals

• Look for those signatures to assess water quality

The Results:

• Assessment – Sensitivity and information-rich measurement of "bio-active" titers.

• Diagnosis – Enhanced understanding of the mechanisms of toxicity and a better assessment of risk.

• Combining the evaluation of human and ecological risks.

• The Goal: New regulatory standards that take advantage of these inexpensive, information-rich approaches.

Dr. John ColbourneAssociate Scientist Genomics Director, CGB (IUB)

Barbara HocevarAssistant Professor Department of Pharmacology and ToxicologySchool of Medicine (IUPUI)

Peter CherbasProfessor BiologyDirector, CGB (IUB)

James KlaunigRobert B. Forney Professor Dept. of Pharmacology and Toxicology Director, Center for Environmental Health School of Medicine (IUPUI)

 Lisa KamendulisAssistant Professor Department of Pharmacology and ToxicologySchool of Medicine (IUPUI)

Keith ClayProfessor of Biology Director, IU Research and Teaching Preserve Director, CRES (IUB)

Joseph Shaw Assistant ProfessorSchool of Public and Environmental Affairs (IUB)

The Indiana University Consortium for Environmental Genomics and Toxicology

First Annual Meeting