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Molecular Genetics and Genomics Program at Wake Forest University School of Medicine

Suzy Torti
Associate Professor of Biochemistry 

B.A., 1970 Reed College, Portland, OR 
Ph.D., 1977 Tufts University, Boston, MA 

Our laboratory is interested in relationships between iron metabolism and tumor growth. One of our active areas of investigation is the use of iron chelators as anti-tumor therapeutics. Recent work in our laboratory suggests that tachpyridine, a novel iron chelator, may function to inhibit tumor growth in vitro and in vivo. We have found that tachpyridine triggers apoptosis in tumor cells by targeting iron metabolism, and are currently investigating pathways of apoptosis induced by tachpyridine, and the role of the tumor suppressor p53 in this response. We are also exploring mechanisms of cell death triggered by chemically related as well as chemically unrelated metal chelators. A related interest in the laboratory is in chemoprevention. Chemoprevention is the use of natural or synthetic compounds to prevent cancer. One way in which chemopreventive agents function is by inducing the synthesis of cytoprotective proteins. Our laboratory has begun to investigate the role of ferritin, a protein that sequesters iron and limits its availability to catalyze deleterious oxygen free radical formation, in this cytoprotective response. We have observed that oltipraz, a prototypic chemopreventive agent, induces ferritin in vivo and in vitro. Using transient transfection of chimeric genes and analysis of nuclear proteins, we are currently assessing the mechanism of this response. In addition, in ollaboration with Dr. M. Welker in the Chemistry Department of WFU, we are testing the ability of novel oxathiolene oxides to function as chemopreventive agents. We have also begun to assess mechanisms by which naturally occurring compounds in foods can serve as chemopreventive agents. These projects directly relate laboratory research to issues of cancer prevention and treatment.  


Recent Publications (selected):

Tsuji, Y., Moran, E., Torti, S.V., and Torti, F. M.: Transcriptional regulation of the mouse ferritin H gene. Involvement of p300/CBP adaptor proteins in FER-1 enhancer activity. J. Biol. Chem. 274:7501-7507 (1999).

Orino, K., Tsuji, Y., Torti, F.M., and Torti, S. V.: Adenovirus E1A blocks oxidant-dependent ferritin induction and sensitizes cells to pro-oxidant cytotoxicity, FEBS Lett., 461:334-338, (1999).

Tsuji, Y., Ayaki, H., Whitman, S.P., Morrow, C.S., Torti, S.V. and Torti, F.M.: Coordinate transcriptional and translational regulation of ferritin in response to oxidative stress, Molec. Cell. Biol., 20:5818-5827, (2000).

Orino, K., Lehman, L., Tsuji, Y., Ayaki, H., Torti, S.V., Torti, F.M. Ferritin and the response to oxidative stress. Biochemical J. 357:241-247, (2001).

Abeysinghe, R.D., Greene, B., Haynes, R., Willingham, M.C., Turner, J., Planalp, R.P., Brechbiel, M.W., Torti, F.M., Torti, S.V.: p53-independent apoptosis mediated by tachpyridine, an anti-cancer iron chelator, Carcinogenesis, 22:1607-1614, (2001).

Torti, S.V., Golden-Fleet, M., Willingham, M.C., Ma, R., Cline, M., Sakimoto, Y., and Torti, F.M. Use of green fluorescent protein to measure tumor growth in an implanted bladder tumor model. J. Urol. 167:724-728, (2002).

Torti, F.M., and Torti, S.V.: Regulation of ferritin genes and proteins. Blood 99:3505-3516, (2002).

Greene, B., Thorburn, J., Thorburn, A., Planalp, R.P., Brechbiel, M.W., Jennings-Gee, J., Wilkinson, J., Torti, F.M. and Torti, S.V.: Activation of caspase pathways during iron chelator-mediated apoptosis, J. Biol. Chem., Apr 29 2002.