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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
Office:
VB / Room 410
Email:
Phone:
979-845-5988
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. Jung, YS, Lee, HS, Cho, HR, Kim, KJ, Kim, JH, Safe, S et al.. Dual targeting of Nur77 and AMPKα by isoalantolactone inhibits adipogenesis in vitro and decreases body fat mass in vivo. Int J Obes (Lond). 2018; :.
    doi: 10.1038/s41366-018-0276-x. PubMed PMID:30538281. .

  2. Wu, CS, Wei, Q, Wang, H, Kim, DM, Balderas, M, Wu, G et al.. Protective effects of ghrelin on fasting-induced muscle atrophy in aging mice. J. Gerontol. A Biol. Sci. Med. Sci. 2018; :.
    doi: 10.1093/gerona/gly256. PubMed PMID:30407483. .

  3. Lacey, A, Hedrick, E, Cheng, Y, Mohankumar, K, Warren, M, Safe, S et al.. Interleukin-24 (IL24) Is Suppressed by PAX3-FOXO1 and Is a Novel Therapy for Rhabdomyosarcoma. Mol. Cancer Ther. 2018;17 (12):2756-2766.
    doi: 10.1158/1535-7163.MCT-18-0118. PubMed PMID:30190424. PubMed Central PMC6279487.

  4. Karki, K, Harishchandra, S, Safe, S. Bortezomib Targets Sp Transcription Factors in Cancer Cells. Mol. Pharmacol. 2018;94 (4):1187-1196.
    doi: 10.1124/mol.118.112797. PubMed PMID:30115673. PubMed Central PMC6117503.

  5. Popichak, KA, Hammond, SL, Moreno, JA, Afzali, MF, Backos, DS, Slayden, RD et al.. Compensatory Expression of Nur77 and Nurr1 Regulates NF-κB-Dependent Inflammatory Signaling in Astrocytes. Mol. Pharmacol. 2018;94 (4):1174-1186.
    doi: 10.1124/mol.118.112631. PubMed PMID:30111648. PubMed Central PMC6117504.

  6. Hedrick, E, Mohankumar, K, Safe, S. TGFβ-Induced Lung Cancer Cell Migration Is NR4A1-Dependent. Mol. Cancer Res. 2018;16 (12):1991-2002.
    doi: 10.1158/1541-7786.MCR-18-0366. PubMed PMID:30072581. .

  7. 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. PubMed Central PMC6138555.

  8. 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. PubMed Central PMC6234016.

  9. 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.

  10. 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.

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