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Steven Safe

Safe, Steven
Steven Safe
Distinguished Professor of Veterinary Physiology and Pharmacology and of Biochemistry and Biophysics Syd Kyle Chair in Veterinary Medicine
VB / Room 410
Undergraduate Education
B.S. Queens University (1962)
Graduate Education
D.Phil. Oxford University (1966)
Postdoc. Oxford and Harvard Universities (1966-68)
Joined Texas A&M in 1981

Molecular Biology of Endocrine Disruption Chemicals

The aryl hydrocarbon receptor (AhR) is a nuclear helix-loop-helix transcription factor which forms a ligand-induced nuclear heterodimer with the AhR nuclear translocator (Arnt) protein. Research in this laboratory is focused on the molecular mechanism of crosstalk between the AhR and estrogen receptor (ER) signaling pathways in which the AhR inhibits estrogen-induced gene expression. The antiestrogenic activities of some AhR agonists are also being developed as drugs for clinical treatment of breast and endometrial cancers in women. Research on estrogen-dependent gene expression in various cancer cell lines is focused on analysis of several gene promoters to determine the mechanisms of ERa and ERb action. This includes several genes that are activated through interactions of the ER with Sp1 protein and other DNA-bound transcription factors.

Recent Publications

  1. Afzali, MF, Popichak, KA, Burton, LH, Klochak, AL, Wilson, WJ, Safe, S et al.. A novel diindolylmethane analog, 1,1-bis(3'-indolyl)-1-(p-chlorophenyl) methane, inhibits the tumor necrosis factor-induced inflammatory response in primary murine synovial fibroblasts through a Nurr1-dependent mechanism. Mol. Immunol. 2018;101 :46-54.
    doi: 10.1016/j.molimm.2018.05.024. PubMed PMID:29870816. .

  2. Jin, UH, Karki, K, Kim, SB, Safe, S. Inhibition of pancreatic cancer Panc1 cell migration by omeprazole is dependent on aryl hydrocarbon receptor activation of JNK. Biochem. Biophys. Res. Commun. 2018;501 (3):751-757.
    doi: 10.1016/j.bbrc.2018.05.061. PubMed PMID:29758193. .

  3. Mohankumar, K, Lee, J, Wu, CS, Sun, Y, Safe, S. Bis-Indole-Derived NR4A1 Ligands and Metformin Exhibit NR4A1-Dependent Glucose Metabolism and Uptake in C2C12 Cells. Endocrinology. 2018;159 (5):1950-1963.
    doi: 10.1210/en.2017-03049. PubMed PMID:29635345. PubMed Central PMC5888234.

  4. Hammond, SL, Popichak, KA, Li, X, Hunt, LG, Richman, EH, Damale, PU et al.. The Nurr1 Ligand,1,1-bis(3'-Indolyl)-1-(p-Chlorophenyl)Methane, Modulates Glial Reactivity and Is Neuroprotective in MPTP-Induced Parkinsonism. J. Pharmacol. Exp. Ther. 2018;365 (3):636-651.
    doi: 10.1124/jpet.117.246389. PubMed PMID:29626009. PubMed Central PMC5941193.

  5. Draz, H, Goldberg, AA, Tomlinson Guns, ES, Fazli, L, Safe, S, Sanderson, JT et al.. Autophagy inhibition improves the chemotherapeutic efficacy of cruciferous vegetable-derived diindolymethane in a murine prostate cancer xenograft model. Invest New Drugs. 2018; :.
    doi: 10.1007/s10637-018-0595-8. PubMed PMID:29607466. .

  6. Jin, UH, Park, H, Li, X, Davidson, LA, Allred, C, Patil, B et al.. Structure-Dependent Modulation of Aryl Hydrocarbon Receptor-Mediated Activities by Flavones. Toxicol. Sci. 2018; :.
    doi: 10.1093/toxsci/kfy075. PubMed PMID:29584932. .

  7. Safe, S, Abbruzzese, J, Abdelrahim, M, Hedrick, E. Specificity Protein Transcription Factors and Cancer: Opportunities for Drug Development. Cancer Prev Res (Phila). 2018; :.
    doi: 10.1158/1940-6207.CAPR-17-0407. PubMed PMID:29545399. .

  8. Choudhary, M, Safe, S, Malek, G. Suppression of aberrant choroidal neovascularization through activation of the aryl hydrocarbon receptor. Biochim. Biophys. Acta. 2018;1864 (5 Pt A):1583-1595.
    doi: 10.1016/j.bbadis.2018.02.015. PubMed PMID:29481912. PubMed Central PMC5880720.

  9. Cheng, Y, Imanirad, P, Jutooru, I, Hedrick, E, Jin, UH, Rodrigues Hoffman, A et al.. Role of metastasis-associated lung adenocarcinoma transcript-1 (MALAT-1) in pancreatic cancer. PLoS ONE. 2018;13 (2):e0192264.
    doi: 10.1371/journal.pone.0192264. PubMed PMID:29389953. PubMed Central PMC5794178.

  10. Safe, S, Nair, V, Karki, K. Metformin-induced anticancer activities: recent insights. Biol. Chem. 2018;399 (4):321-335.
    doi: 10.1515/hsz-2017-0271. PubMed PMID:29272251. .

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