Reasearch Interests

In our laboratory, we consider the molecular origins of disease as a problem in fundamental cellular and environmental genetics: both genetic and environmental risk factors interact to determine the phenotype and health of an individual. The human genome is subject to continuous environmental challenge. This genotoxic exposure constitutes a significant determinant of disease incidence; for example, progressive genome instability is diagnostic of tumorigenesis. At the cellular level, variation in an individual's sensitivity to environmental insult reflects allelic differences in the genes and pathways that function to maintain genome stability and to provide cellular homeostasis. The cellular response to environmental challenge is phenotypically complex and its inherited component is correspondingly multigenic. Approximately 12% of the genes identified in the Human Genome Project have been functionally classified as required for "organism defense and homeostasis". Identification of the susceptibility genes that confer cellular sensitivity to exogenous stress will provide valuable inherited risk factors for complex environmentally responsive diseases such as cancer, diabetes, and neurodegenerative disorders. Our research combines a functional genomics approach using the yeast model with high throughput cellular, genetic, and molecular diagnostic assays to investigate both the genetic control of genome stability and the cellular pathways that protect against environmental insult. 

Selected Publications

Giroux, C.N., Wang, Y., and Weiss, A (2002). A yeast functional genomics model for the cellular response to oxidative stress. The Toxicologist 66 (1-S): 19. Published abstract presented at the Society of Toxicology Annual Meeting.

Arking, R. and Giroux, C.N. (2001). Antioxidant genes, hormesis, and demographic selection, Journal of Anti-Aging Medicine 4: 25-36.

Ramos, W., Liu, G., Giroux, C.N., and Tomkinson, A.E. (1998). Biochemical and Genetic Characterization of the DNA Ligase Encoded by Saccaromyces Cerevisiae Open Reading Frame YOR005c, a Homolog of Mammalian DNA Ligase IV, Nucleic Acids Research, 26: 5676-5683.

Keeney, S., Giroux, C.N., and Kleckner, N. (1997). Meiosis-Specific DNA Double-Strand Breaks are Catalyzed by Spo11, a Member of a Widely Conserved Protein Family. Cell. 88: 375-384.