I am interested in the redox regulation of gene expression. Oxidative stress is a component of many human diseases and contributes to the toxicity of a number of environmental and therapeutic agents. Furthermore, the generation of small amounts of pro-oxidants appears to be an essential part of several signal transduction pathways. Although all macromolecules can be targets of oxidative damage, the oxidation of specific cysteine thiols in some proteins (such as transcription factors) can have dramatic functional consequences. Thioredoxin is a redox-active protein that is ideally suited for the reduction of oxidized cysteine residues in proteins, providing a means by which oxidative signals can be reversed. The major goal of my research is to define the roles of thioredoxin in oxidative signaling in the cytoplasm and as a regulator of gene expression in the nucleus.

Environmental Health Sciences, redox, thioredoxin, toxicology, oxidative stress, nucleocytoplasmic transport

Halvey, PJ, Watson, WH, Hansen, JM, Go, YM, Samali, A, Jones, DP. Compartmental oxidation of thiol-disulfide redox couples during epidermal growth factor signalling. Biochem. J. 386: 215-219, 2005.

Hansen, JM, Watson, WH, and Jones, DP. Compartmentation of Nrf-2 redox control: Regulation of cytoplasmic activation by glutathione and DNA binding by thioredoxin-1. Tox. Sci. 82: 308-317, 2004.

Watson, WH, Yang, X, Choi YE, Jones, DP, and Kehrer, JP. Thioredoxin and its role in toxicology. Tox. Sci. 78: 3-14, 2004.

Watson, WH, Pohl, J, Montfort, WR, Stuchlik, O, Reed, MS, Powis, G, and Jones, DP. Redox potential of human thioredoxin 1 and identification of a second dithiol/disulfide motif. J. Biol. Chem. 278: 33408-33415, 2003.

Watson, WH, and Jones, DP. Oxidation of nuclear thioredoxin during oxidative stress. FEBS Lett. 543: 144-147, 2003.

Watson, WH, Chen, Y, and Jones, DP. 2003. Redox state of glutathione and thioredoxin in differentiation and apoptosis. BioFactors. 17: 307-314, 2003.

Watson, WH, Dahm, LJ, and Jones, DP. Mechanisms of chemically-induced liver disease. In: Hepatology, Zakim and Boyer (Ed.), 4th ed., Saunders: Philadelphia, 2003.

Nkabyo, YS, Ziegler, TR, Gu, LH, Watson, WH, and Jones DP. Glutathione and thioredoxin redox during differentiation in human colonic epithelial (Caco-2) cells. Am. J. Physiol. Gastrointest. Liver Physiol. 283: G1352-G1359, 2002.

Miller, LT, Watson, WH, Kirlin, WG, Zeigler TR, and Jones, DP. Oxidation of GSH/GSSG redox state induced by cysteine deficiency in human colon carcinoma HT29 cells. J Nutr 132: 2303-2306, 2002

McClain, CJ, Hill, DB, Song, Z, Chawla, R, Watson, WH, Chen, T, and Barve, S. S-Adenosylmethionine, cytokines, and alcoholic liver disease. Alcohol 27: 185, 2002.

Tsukamoto, H, Takei Y, McClain, CJ, Joshi-Barve, S, et al. How is the liver primed or sensitized for alcoholic liver disease? Alcohol Clin. Exp. Res. 25: 171S-181S, 2001.

Watson, WH, Cai, J, and Jones, DP. Diet and apoptosis. Annu. Rev. Nutr. 20: 485-505, 2000.

Watson, WH, Zhao, Y, and Chawla, RK. S-Adenosylmethionine attenuates the lipopolysaccharide-induced expression of the gene tumor necrosis factor á. Biochem J 342:21-25, 1999.

Chawla, RK, Watson, WH, Eastin, CE, Lee, EY, Schmidt, J, and McClain, CJ. S-Adenosyl-methionine deficiency and TNF-alpha in lipopolysaccharide-induced hepatic injury.Am J Physiol 275: G125-G129, 1998.

Chawla, RK, Watson, WH, and Jones, DP. Effect of Hypoxia on Hepatic DNA Methylation and tRNA Methyltransferase in Rat: Similarities to Effects of Methyl-Deficient Diets. J Cell Biochem 61: 72-80, 1996.