EDUCATION:

• B.Sc., Queen's University, 1962
• M.Sc., Queen's University, 1963
• D. Phil., Oxford University, 1965

SPECIALTY AREAS:

• Biochemistry
• Toxicology

PREVIOUS EMPLOYMENT:

• Research Office, NRC - Canada
• Professor, University of Guelph
• Distinguished Professor, Texas A&M University
• Sid Kyle Chair in Toxicology

HONORS:

PROFESSIONAL SOCIETIES:

• Chemical Institute of Canada
• Canadian Federation of Biological Societies
• American Association for Cancer Research
• American Society for Mass Spectrometry
• American College of Toxicology
• American Chemical Society
• The Chemical Society
• Canadian Society for Toxicology
• Sigma Xi
• International Society for the Study of Xenobiotocs
• Society of Toxicology

SELECTED RESEARCH PUBLICATIONS (last 2 years):

• Stewart, D.M., Johnson, G.A., Vyhlidal, C.A., Burghardt, R.C., Safe, S., Yu-Lee, L.-Y., Bazer, F.W., and Spencer, T.E.  Interferon tao activates multiple signal transducer and activator of transcription proteins and has complex effects on interferon-responsive gene transcription in ovine endometrial epithelial cells.  Endocrinology  142:98-107, 2001.
• Wang, F., Samudio, I., and Safe, S.  Transcriptional activation of cathepsin D gene expression by 17beta-estradiol:  mechanism of aryl hydrocarbon receptor-mediated inhibition.  Mol. Cell. Endocrinol.  172:91-103, 2001.
• Porter, W., Wang, F., Duan, R., Qin, C., Castro-Rivera, E., and Safe, S.  Transcriptional activation of heat shock protein 27 gene expression by 17beta-estradiol and modulation by antiestrogens and aryl hydrocarbon receptor agonists:  estrogenic activity of ICI 164,384.  J. Mol. Endocrinol.  26:31-42, 2001.
• Chen, I., Hsieh, T., Thomas, T., and Safe, S.  Mechanisms of inhibitory aryl hydrocarbon receptor-estrogen receptor crosstalk in MCF-7 breast cancer cells:  identification of genes downregulated by AhR agonists using suppression subtractive hybridization.  Gene  262:207-214, 2001.
• Samudio, I., Vyhlidal, C., Wang, F., Stoner, M., Chen, I., Kladde, M., Barhoumi, R., Burghardt, R., and Safe, S.  Transcriptional activation of DNA polymerase alpha gene expression in MCF-7 cells by 17beta-estradiol.  Endocrinology  142:1000-1008, 2001.
• Duan, R., Xie, W., Burghardt, R., and Safe, S.  Estrogen receptor-mediated activation of the serum response element in MCF-7 cells through MAPK-dependent phosphorylation of Elk-1.  J. Biol. Chem.   276:11590-11598, 2001.
• Qin, C., Wilson, C., Blancher, C., Taylor, M., Safe, S., and Harris, A.  Association of ARNT splice variant with estrogen receptor-negative breast cancer, poor induction of vascular endothelial growth factor under hypoxia and poor prognosis.  Clin. Cancer Res.  7:818-823, 2001.
• Safe, S.  Molecular biology of the Ah receptor and its role in carcinogenesis.  Toxicol. Lett.  120:1-7, 2001.
• McDougal, A., Gupta, M.S., Morrow, D., Ramamoorthy, K., Lee, Y.-E., and Safe, S.  Methyl-substituted diindolylmethanes as inhibitors of estrogen-induced growth of T47D cells and mammary tumors in rats.  Breast Cancer Res. Treat.  66:147-157, 2001.
• McDougal, A., Wormke, M., Calvin, J., and Safe, S.  Tamoxifen-induced antitumorigenic/antiestrogenic action synergized by a selective Ah receptor modulator.  Cancer Res.  61:3901-3907, 2001.
• Xie, W., Duan, R., and Safe, S.  Activation of adenosine deaminase in MCF-7 cells through insulin-like growth factor-estrogen receptor alpha crosstalk.  J. Mol. Endocrinol.   26:217-228, 2001.
• Sanderson, J.T., Slobbe, L., Lansbergen, G.W.A., Safe, S., and Van den Berg, M.  2,3,7,8-Tetrachlorodibenzo-p-dioxin and diindolylmethanes differentially induce cytochrome P450 1A1, 1B1, and 19 in H295R human adrenocortical carcinoma cells.  Toxicol. Sci  61:40-48, 2001.
• Castro-Rivera, E., Samudio, I., and Safe, S.  Estrogen regulation of cyclin D1 gene expression in ZR-75 breast cancer cells involves multiple enhancer elements.  J. Biol. Chem.  276:30853-30861, 2001.
• Waters, K.M., Safe, S., and Gaido, K.W.  Differential gene expression in response to methoxychlor and estradiol through ERalpha, ERbeta, and AR in reproductive tissues of female mice.  Toxicol. Sci.  63:47-56, 2001.
• Safe, S., Pallaroni, L., Yoon, K., Gaido, K., Ross, S., Saville, B., and McDonnell, D.  Toxicology of environmental estrogens.  Reprod. Fertil. Dev.  13:307-315, 2001.
• Yoon, K., Pallaroni, L., Stoner, M., Gaido, K., and Safe, S.  Differential activation of wild-type and variant forms of estrogen receptor alpha by synthetic and natural estrogenic compounds using a promoter containing three tandem estrogen-responsive elements.  J. Ster. Biochem. Mol. Biol.  78:25-32, 2001.
• Safe, S., McDougal, A., Gupta, M.S., and Ramamoorthy, K.  Selective Ah receptor modulators (SAhRMs):  progress towards development of a new class of inhibitors of breast cancer growth.  J. Women's Cancer  3:37-45, 2001.
• Safe, S.  Transcriptional activation of genes by 17beta-estradiol through estrogen receptor-Sp1 interactions.  Vitam. Horm.  62:231-252, 2001.
• Lee, J.-E. and Safe, S.  Inhibition of CYP1A1 expression by resveratrol in breast cancer cells involves a post-transcriptional mechanism.  Biochem. Pharmacol.  62:1113-1124, 2001.
• Wang, F. and Safe, S.  Transcriptional activation of rat creatine kinase B by 17beta-estradiol in MCF-7 cells involves and estrogen responsive element and GC-rich sites.  J. Cell Biochem.  84:156-172, 2002.
• Saville, B., Poukka, H., Wormke, M., Jänne, O.A., Palvimo, J.J., Stoner, M., Samudio, I., and Safe, S.  Cooperative coactivation of estrogen receptor alpha in ZR-75 human breast cancer cells by SNURF and TATA-binding protein.  J. Biol. Chem.  277:2485-2497, 2002.
• Mealey, K.L., Barhoumi, R., Burghardt, R.C., Safe, S., and Kochevar, D.T.  Doxycycline induces expression of P glycoprotein in MCF-7 breast carcinoma cells.  Antimicrob. Agents Chemother.  46:755-761, 2002.
• Duan, R., Xie, W., Li, X., McDougal, A., and Safe, S.  Estrogen regulation of c-fos gene expression through phosphatidylinositol-3-kinase-dependent activation of serum response factor in MCF-7 breast cancer cells.  Biochem. Biophys. Res. Commun.  294:384-394, 2002.
• Qin, C., Nguyen, T., Stewart, J., Samudio, I., Burghardt, R., and Safe, S.  Estrogen upregulation of p53 gene expression in MCF-7 breast cancer cells is mediated by calmodulin kinase IV-dependent activation of an NFkB/CTF-1 complex.  Mol. Endocrinol.  16:1793-1809, 2002.
• Barhoumi, R., Mouneimne, Y., Awooda, I., Safe, S., Donnelly, K.C., and Burghardt, R.C.  Characterization of calcium oscillations in normal and benzo[a]pyrene-treated Clone 9 cells.  Toxicol. Sci.   68:444-450, 2002.
• Abdelrahim, M., Samudio, I., Smith, R., Burghardt, R., and Safe, S.  Small inhibitory RNA duplexes for Sp1 mRNA block basal and estrogen-induced gene expression and cell cycle progression in MCF-7 breast cancer cells.  J. Biol. Chem.  277:28815-28822, 2002.
• Stoner, M., Saville, B., Wormke, M., Dean, D., Burghardt, R., and Safe, S.  Hypoxia induces proteasome-dependent degradation of estrogen receptor alpha in ZR-75 breast cancer cells.  Mol Endocrinol  16:2231-2242, 2002.
• Koliopanus, A. Kleeff, J., Xiao, Y., Safe, S., Zimmerman, A., Buchler, M.W. and Friess, H.  Increased aryl hydrocarbon receptor expression offers a potential therapeutic target in pancreatic cancer.  Oncogene  21:6059-6070, 2002.
• Safe, S. and McDougal, A.  Mechanism of action and development of selective aryl hydrocarbon receptor modulators for treatment of hormone-dependent cancers.  Int. J. Oncol.  20:1123-1128, 2002.
• Vyhlidal, C., Li, X. and Safe, S.  Estrogen regulation of transferrin gene expression in MCF-7 human breast cancer cells.  J. Mol. Endocrinol.  29:305-317, 2002.
• Avakian, M.D., Dellinger, B.; Fiedler, H., Gullet, B., Koshland, C., Marklund, S., Oberdorster, G., Safe, S., Sarofim, A., Smith, K.R., Schwartz, D. and Suk, W.A.  The origin, fate, and health effects of combustion by-products:  a research framework.  Environ. Health Persp.  110:1155-1662, 2002.
• Safe, S., Pallaroni, L., Yoon, K., Gaido, K., Ross, S. and McDonnell, D.  Problems for risk assessment of endocrine-active estrogenic compounds.  Environ. Health Perspect.  110(S):925-929, 2002.
• Safe, S.  Environmental estrogens:  roles in male reproductive tract problems and in breast cancer.  Rev. Environ. Health  17:253-262, 2002.
• Wormke, M., Stoner, M., Saville, B., Walker, K., Abdelrahim, M., Burghardt, R., and Safe, S.  The aryl hydrocarbon receptor mediates degradation of the estrogen receptor alpha through activation of proteasome.  Mol. Cell. Biol.  23:1843-1855, 2003.
• Qin, C., Burghardt, R., Smith, R., Wormke, M., Stewart, J. and Safe, S.  Peroxisome proliferator-activated receptor gamma agonists induce proteasome-dependent degradation of cyclin D1 and estrogen receptor alpha in MCF-7 breast cancer cells.  Cancer Res.  63:958-964, 2003.
• Safe, S., Yoon, K., Castro-Rivera, E., Pallaroni, L. and Gaido, K.  Ligand structure-dependent activation of the estrogen receptor by xenoestrogens.  Frontiers in Biosciences  in press, 2003.
• Castro-Rivera, E. and Safe, S.  17beta-Estradiol- and 4-hydroxytamoxifen-induced transactivation in breast, endometrial and liver cancer cells is dependent on ER-subtype, cell and promoter context.  J. Ster. Biochem. Mol. Biol.  84:23-31, 2003.
• Ngwenya, S. and Safe, S.  Cell context-dependent differences in the induction of E2F-1 gene expression by 17beta-estradiol in MCF-7 and ZR-75 cells.  Endocrinology  144:1675-1685, 2003.
• Khan, S., Abdelrahim, M., Samudio, I. and Safe, S.  Estrogen receptor/Sp1 complexes are required for induction of cad gene expression by 17beta-estradiol in breast cancer cells.  Endocrinology  144:2325-2335, 2003.
• Kim, K., Thu, N., Saville, B. and Safe, S.  Domains of estrogen receptor alpha (ERalpha) required for ERalpha/Sp1-mediated activation of GC-rich promoters by estrogens and antiestrogens in breast cancer cells.  Mol. Endocrinol.  17:804-817, 2003.
• Abdelrahim, M., Smith III, R. and Safe, S.  Aryl hydrocarbon receptor gene silencing with small inhibitory RNA differentially modulates Ah-responsiveness in MCF-7 and HepG2 cancer cells.  Mol. Pharmacol.  63:1373-1381, 2003.
• Safe, S. and Wormke, M.  Inhibitory aryl hydrocarbon-estrogen receptor alpha crosstalk and mechanisms of action.  Chem. Res. Toxicol.  16:807-816, 2003.
• Zhang, S., Qin, C. and Safe, S.  Flavonoids as aryl hydrocarbon receptor agonists/antagonists effects of structure and cell context.  Environ. Health Persp.  111:1877-1882, 2003.
• Zhang, W., Jiang, J., Qin, C., Thomson, L.M., Parrish, A.R., Safe, S.H. and Simanek, E.E.  Triazine dendrimers for drug delivery:  evaluation of solubilization properties, activity in cell culture, and in vivo toxicity of a candidate vehicle.  Supramolecular Chem.  15:607-616, 2003. 
• Stoner, M., Wormke, M., Saville, B., Samudio, I., Qin, C., Abdelrahim, M. and Safe, S.  Estrogen regulation of vascular endothelial growth factor gene expression in ZR-75 breast cancer cells through interaction of estrogen receptor alpha and Sp proteins.  Oncogene  23:1052-1063, 2004.
• Morrow, D., Qin, C., Smith III, R. and Safe, S.  Aryl hydrocarbon receptor-mediated inhibition of LNCaP prostate cancer cell growth and hormone-induced transactivation.  J. Ster. Biochem. Mol. Biol.  88:27-36, 2004.
• Cizmas, L., Zhou, G-D., Safe, S.H., McDonald, T.J., Zhu, L. and Donnelly, K.C.  Comparative in vitro and in vivo genotoxicities of 7H-benzo[c]fluorene, manufactured gas plant residue (MGP), and MGP fractions.  Environ. Mol. Mutagen.  43:159-168, 2004.
• Qin, C., Morrow, D., Stewart, J., Spencer, K., Porter, W., Smith III, R., Phillips, T., Abdelrahim, M., Samudio, I. and Safe, S.   A new class of peroxisome proliferator-activated receptor gamma (PPARgamma) agonists that inhibit growth of breast cancer cells:  1,1-bis(3'-indolyl)-1-(p-substitutedphenyl)methanes.  Mol. Cancer Therap.  3:247-259, 2004.
• Pearce, S.T., Liu H., Radhakrishnan, Abdelrahim, M., Safe, S. and Jordan, V.C.  Interaction of the aryl hydrocarbon receptor ligand 6-methyl-1,3,8-trichlorodibenzofuran (MCDF) with estrogen receptor.  Cancer Res.  64:289-2897, 2004.
• Corbin, C.J., Mapes, S.M., Marcos, J., Shackleton, C.H., Morrow, D., Safe, S., Wise, T., Ford, J.J. and Conley, J.  Paralogues of porcine aromatase cytochrome P450:  a novel hydroxylase activity and the survival of a duplicated gene.  Endocrinology  145:2157-2164, 2004.
• Safe, S. and Kim, K.  Nuclear receptor-mediated transactivation through interactions with Sp proteins.  Prog. Nucl. Acids Res. Mol. Biol.  77:1-36, 2004.
• Qin, C., Samudio, I., Ngwenya, S. and Safe, S.  Estrogen-dependent regulation of ornithine decarboxylase in breast cancer cells through activation of non-genomic cAMP-dependent pathways.  Mol. Carcin.  40:160-170, 2004.
• Li, X., Qin, C., Burghardt, R. and Safe, S.  Hormonal regulation of lactate dehydrogenase A through activation of protein kinase C pathways in MCF-7 breast cancer cells.  Biochem. Biophys. Res. Commun.  320:625-634, 2004.
• Chintharlapalli, S., Smith III, R., Samudio, I., Zhang, W., Safe, S.  1,1-Bis(3'-indolyl)-1-(p-substituted-phenyl)methanes induce peroxisome proliferator-activated receptor gamma-mediated growth inhibition, transactivation and differentiation markers in colon cancer cells.  Cancer Res.  in press, 2004.