Dr. Suzy Torti

Associate Professor of Biochemistry
B.A., Reed College, 1970
Ph.D. (Molecular Biology and Microbiology), Tufts University, 1977
Telephone:(336)716-9948; E-mail: storti@wfubmc.edu

Our laboratory is interested in relationships between iron metabolism and tumor growth. This interest generates 3 current projects:

(1) Natural and synthetic cancer chemopreventives and their relationship to iron chelation. Curcumin is a naturally-occurring compound that has been used for centuries as a medicinal and coloring agent. Curcumin is among the more successful chemopreventive agents investigated in recent years, and is currently in human trials to prevent cancer. We have made the unexpected observation that curcumin strikingly modulates proteins of iron metabolism in cultured cells and in mouse liver: curcumin represses ferritin protein, increases transferrin receptor, and activates IRP, all indicators of iron depletion. These results suggest that iron chelation may be a mode of action of curcumin, a result that may have important implications for the use of this and other agents in cancer chemoprevention. We are currently conducting experiments in tissue culture and animal models to further explore this hypothesis. In related studies, we are collaborating with Dr. M. Welker in the Chemistry Department of Wake Forest University to test the activity of new classes of synthetic chemopreventive agents.

(2) Cancer angiogenesis and iron metabolism. Angiogenesis plays a key role in tumor growth, since the appropriate delivery of nutrients through blood vessels is important to tumor growth and oxygenation. In addition, agents that normalize tumor vasculature can enhance the delivery of anti-tumor agents. We have discovered that ferritin, a protein best known for its iron storage and detoxification properties, has an additional, less well-studied property: it regulates processes in angiogenesis. It does so by an interaction with HKa, an anti-angiogenic protein that induces apoptosis (programmed cell death) in vascular endothelial cells. We have observed that ferritin inhibits the pro-apoptotic effect of HKa on vascular endothelial cells. We are currently investigating the structural requirements of this interaction and its consequences on cell survival signaling pathways. Over the long term, these studies may suggest novel targets for modulating angiogenesis in vivo.

(3) A novel bone morphogenetic protein antagonist in cancer. We have identified a novel protein termed BARC (BMP Antagonist Regulated in Cancer) that is down-regulated in several types of cancer, including kidney cancer and breast cancer. We have shown that this protein is secreted, and may affect tumor cells by modulating signaling by BMP proteins (bone morphogenic proteins). Current studies are exploring the hypothesis that this protein is a new tumor suppressor.

Updated June 2006

Recent Publications

1. Pham, C. G., Bubici, C., Zazzeroni, F., Papa, S., Jones, J., Alvarez, K., Jayawardena, S., De Smaele, E., Cong, R., Beaumont, C., Torti, F. M., Torti, S. V., Franzoso, G.: Ferritin heavy chain upregulation by NF-kappaB inhibits TNFalpha-induced apoptosis by suppressing reactive oxygen species. Cell 119:529-542, 2004.

2. Turner, J.L., Koumenis, C., Kute, T.E., Planalp, R.P., Brechbiel, M.W., Beardsley, D., Cody, B., Brown K.D., Torti, F.M., and Torti S.V. Tachpyridine, a metal chelator, induces G2 cell cycle arrest, activates checkpoint kinases, and sensitizes cells to ionizing radiation. Blood 106:3191-9, 2005.

3. Torti, S.V., Ma, R., Venditto, V.J., Torti, F.M., Planalp, R.P., Brechbiel. Preliminary Evaluation of the cytotoxicity of a series of tris-2-aminoethylamine (tren) based hexadentate heterocyclic donor agents. Bioorg. Med. Chem. 13:5961-7, 2005.

4. Wilkinson, J., Di, X., Schonig, K., Buss, J.L., Kock, N.D., Cline, J.M, Saunders, T.L, Bujard, H., Torti, S.V., Torti, F.M. Tissue-specific expression of ferritin H regulates cellular iron homeostasis in vivo. Biochem J. 395:501-7, 2006.

5. Jiao, Y., Wilkinson, J. 4th, Pietsch, C.E., Buss, J.L., Wang, W., Planalp, R., Torti, F.M., Torti, S.V. Iron chelation in the biological activity of curcumin. Free Radic. Biol. Med. 40:1152-60, 2006.

6. Jennings-Gee, J.E., Tsuiji, Y., Pietsch, E.C., Moran, E., Mymryk, J.S., Torti, F.M., Torti, S.V. Coordinate inhibition of cytokine-mediated induction of ferritin H, MNSOD and IL-6 by the adenovirus E1A oncogene. J. Biol. Chem. 281:16428-35, 2006.