US EPA

Completion of genome sequencing for humaris, rodents and various model organisms provides opportunities for hierarchical classification of genes into families, subfamilies, and their chromosomal localization. This classification is a valuable tool in pinpointing candidate disease genes within loci that are associated with various gene families. By similar exercise with a cross species comparison approach we are tapping knowledge on molecular signaling pathways involved in neurodegenerative and cardiovascular disease from model organisms such as Drosophila and Zebrafish. The simple and most common adaptive response mechanism to oxidative stress appears to be up-regulation of antioxidant proteiils and detoxification enzymes. The leucine zipper family of transcription factors (Nrfl and Nrf2) has been recognized as the principal mediators of up-regulation of these cytoprotective genes in mammals and C. elegans suggesting that this pathway may be conserved across the species. Integrating comparative cross species genomics approaches promises accelerated identification of conserved ROS-mediated signaling pathways and second messenger systems. This presentation will explore whether such an approach lead to defining and scoring oxidative stress by combining redox state and oxidative damage linking to DNA damage, repair, apoptosis, cell proliferation, pro:.. and anti-inflammation signals?

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