Research Program:

A broad goal of my research is aimed at understanding the processes that alter the balance between pro-inflammatory and anti-inflammatory events in lung disease as related to changes in antioxidant defense. The lung is particularly sensitive to the effects of air pollutants, such as ozone, nitrogen dioxide that are direct oxidants. I currently have 2 NIH funded RO1s to look at these processes in Cystic Fibrosis (CF) lung disease and Chronic Beryllium Disease (CBD). In the CF project, my laboratory is examining the role of glutathione (GSH) transport into the lung epithelial lining fluid (ELF) as a factor that modulates lung injury response to oxidants . We have previously reported that CFTR is the predominant GSH transporter in the lung and plays a prominent role in maintaining GSH in the ELF. My laboratory is also currently exploring ways to modulate GSH transport in the lung as potential therapies for a wide range of lung diseases, (such as Pulmonary Fibrosis (IPF) ARDS, and chronic obstructive lung diseases (COPD)), that share this deficit in ELF GSH levels. In the CBD project, we are examining the role of oxidative stress in T cell mediated responses to beryllium. CBD is thought to be a Th1-mediated lung disease with the formation of a granuloma. In addition to these areas, I am actively developing catalytic antioxidant therapeutic agents and currently one of these compounds is in phase I human clinical trials.

Key Publications:

• Day, B.J., Shawen, S., Liochev, S.I. and Crapo, J.D. A metalloporphyrin superoxide dismutase mimetic protects against paraquat-induced endothelial cell injury, in vitro. J Pharmacol Exp Ther 275:1227-1232, 1995.
• Day, B.J., Batinic-Haberle, I., and Crapo, J.D. Metalloporphyrins are potent inhibitors of lipid peroxidation. Free Rad. Biol. Med. 26:730-736, 1999.
• Hildeman, D., Mitchell, T., Teague, T.K., Henson, P., Day, B.J., Kappler, J., and Marrack, P. Reactive oxygen species regulate activation induced T cell apoptosis. Immunity 10:735-744, 1999.
• Day, B.J., Patel, M., Calavetta, L., Chang, L.Y. and Stamler, J.S. A mechanism for paraquat toxicity that involves nitric oxide synthase. Proc. Natl. Acad. Sci. 96:12760-12765, 1999.
• Velsor, L., van Heeckeran, A., and Day, B.J. Antioxidant imbalance in the lungs of the cystic fibrosis transmembrane conductance regulator protein mutant mouse. Am. J. Physiol. 281:L31-L38, 2001.
• Trova, M.P., Gauuan, P.J.F., Pechulis, A.D., Bubb, S.M., Bocckino, S.B., Crapo, J.D. and Day, B.J. Superoxide dismutase mimetics part II: synthesis and structure activity relationship of glyoxylate- and glyoxamide-derived metalloporphyrins. Bioorganic Med. Chem. 11:2695-2707, 2003.
• Day, B.J., van Heeckeren, A.M., Min, E., and Velsor, L., Role for CFTR in a glutathione response to bronchopulmonary pseudomonas infection. Infect. Immun. 72:2045-2051, 2004.
• Sawyer, R.T., Dobis, D.R., Goldstein, M., Velsor, L., Maier, L.A., Fontenot, A.P., Silveira, L., Newman, L.S. and Day B.J. Beryllium-induced reactive oxygen species and macrophage apoptosis. Free Radic. Biol. Med. 38:928-937, 2005.
• Kachadourian, R and Day, B.J. Flavonoid-induced glutathione depletion: potential implications for cancer treatment. Free Radic. Biol. Med. 41:65-76, 2006.

View of Recent Publications in PubMed