Research
My training is in cellular biochemistry and molecular toxicology. I study how cells respond to harmful molecules (e.g., oxidizing agents, transition metals, carbon-based electrophiles) that impair critical processes by damaging DNA and proteins. To counteract the adverse effects of these molecules, most cells adapt by mounting gene expression responses that ultimately help clear the reactive molecules and repair their damaged macromolecular targets. However, if the damage is too severe, cell death is the typical outcome. We utilize baker’s yeast and human cancer cell model systems to define more clearly how individual cells sense and respond to protein-damaging molecules. I enjoy having students help with these projects as part of their Independent Study research or through working as research assistants during the academic year and the summer.
Projects that are ongoing are described below:
(1) Understanding the regulation of stress responsive gene expression in yeast and mammalian cells.
In recent years, my collaborators and I have studied how electrophiles and other thiol reactive molecules trigger various gene expression responses in different eukaryotic models. Ongoing work is focused on the sensor proteins that become modified to trigger these responses and determining the interplay/influences of these responses on one another.
Representative publications...
West, J.D., Wang, Y., and Morano, K.A. (2012) Chem. Res. Toxicol. 25, 2036-2053. publisher's site
Wang, Y., Gibney, P.A., West, J.D., and Morano, K.A. (2012) Mol. Biol. Cell 23, 3290-3298. publisher's site
Trott, A., West, J.D., Klaić, L., Westerheide, S.D., Silverman, R.B., Morimoto, R.I., and Morano, K.A. (2008) Mol. Biol. Cell, 19, 1104-1112.publisher's site
West, J.D. and Marnett, L.J. (2006) Chem. Res. Toxicol. 19, 173-194. publisher's site
West, J.D. and Marnett, L.J. (2005) Chem. Res. Toxicol. 18, 1642-1653. publisher's site
(2) Studying the enhanced toxicity of bifunctional electrophiles.
Working with undergraduates at Wooster, we have found that a number of bifunctional electrophiles are considerably more toxic than their monofunctional analogs. These results are correlated with the ability of the bifunctional electrophiles to cross-link target proteins to one another in treated cells. We are currently expanding this study to other types of bifunctional electrophiles and exploring potential mechanisms through which this enhancement of toxicity may be achieved.
Representative publications...
Spencer, M.K., Radzinski, N.P., Tripathi, S., Chowdhury, S., Herrin, R.P., Chandran, N.N., Daniel, A.K., and West, J.D. (2013) Chem. Res. Toxicol. 26, 1720-1729. publisher's site
West, J.D., Stamm, C.E., Brown, H.A., Justice, S.L., and Morano, K.A. (2011) Chem. Res. Toxicol. 24, 1457-1459. publisher's site
West, J.D., Stamm, C.E., and Kingsley, P.J. (2011) Chem. Res. Toxicol. 24, 81-88. publisher's site
(3) Using bifunctional electrophiles as tools for identifying proteins modified by electrophiles in cells and stabilizing specific protein-protein interactions.
We have identified a particular class of redox active proteins (the thioredoxins) in yeast as targets of bifunctional electrophiles. In subsequent work, we found that the thioredoxins become cross-linked to proteins that they function with in a known redox relay. We are currently examining other cellular redox relay proteins to determine whether they are targets of these proteins in addition to studying the significance of thioredoxin modification on a mechanistic level.
Representative publications...
Allan, K.M., Loberg, M.A., Chepngeno, J., Hurtig, J.E., Tripathi, S., Kang, M.G., Allotey, J.K., Widdershins, A.H., Pilat, J.M., Sizek, H.J., Murphy, W.J., Naticchia, M.R., David, J.B., Morano, K.A., and West, J.D. (2016) Free Radic. Biol. Med. 101, 356-366. publisher's site
Naticchia, M.R., Brown, H.A., Garcia, F.J., Lamade, A.M., Justice, S.L., Herrin, R.P., Morano, K.A., and West, J.D. (2013) Chem. Res. Toxicol. 26, 490-497.publisher's site
West, J.D., Stamm, C.E., Brown, H.A., Justice, S.L., and Morano, K.A. (2011) Chem. Res. Toxicol. 24, 1457-1459. publisher's site
Please contact me (jwest-at-wooster.edu) if you are interested in these projects.