My laboratory investigates the response of individuals or populations to toxic or carcinogenic environmental agents. The long-term objective of this work is to elucidate the molecular mechanisms that underlie this response. Many chemical compounds interfere with the control mechanisms that regulate gene expression causing the overexpression of some genes and the repression of others. The ultimate effect of this process is an alteration of the steady-state levels of the proteins encoded by the genes affected. In recent years, however, it has become increasingly clear that this effect varies drastically as a result of genetic differences in the individuals affected. My interests are centered, on the one hand, on the molecular mechanisms of action of these toxic environmental agents, and on the other, on the analysis of genetic diversity in the response to these agents. The genes on which we focus this work are those that code for transcription factors with a regulatory role in the expression of detoxification enzymes.
Strobeck, M., Fribourg, A.F., Puga, A., and Knudsen, E.S.. Restoration of retinoblastoma mediated signaling to cdk2 results in cell cycle arrest. Oncogene 19:1857-1867 (2000).
Puga, A., Barnes, S.J., Dalton, T.P., Chang, C.-Y., Knudsen, E.S. and Maier, A. Aromatic hydrocarbon receptor interaction with the retinoblastoma Protein potentiates Repression of E2F-Dependent Transcription and Cell Cycle Arrest. J. Biol. Chem. 275:2943?2950 (2000).
Puga, A., Barnes, S.J., Chang, C.-Y., Zhu,H., Nephew, K.P., Khan, S.A., and Shertzer, H.G. Activation of transcription factors AP-1 and NF-6B by 2,3,7,8-tetrachlorodibenzo-p-dioxin. Biochem. Pharmacol. 59:997-1005 (2000).
FitzGerald, C.T., Nebert, D.W. and Puga, A. Regulation of mouse Ah receptor gene expression by members of the Sp family of transcription factors. DNA Cell Biol. 17:811-822 (1998).
Maier, A., Micka, J., Miller, K., Denko, T., Chang, C.-Y., Nebert, D.W. and Puga, A. Aromatic hydrocarbon receptor (AHR) polymorphism: development of new methods to correlate genotype with phenotype. Environmental Health Persp. 106:421-426 (1998).
Chang, C.-Y. and Puga, A. Constitutive activation of the aromatic hydrocarbon receptor. Mol. Cell. Biol., 18:525-535 (1998).