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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

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  1. Park, H, Jin, UH, Orr, AA, Echegaray, SP, Davidson, LA, Allred, CD et al.. Isoflavones as Ah Receptor Agonists in Colon-Derived Cell Lines: Structure-Activity Relationships. Chem. Res. Toxicol. 2019; :.
    doi: 10.1021/acs.chemrestox.9b00352. PubMed PMID:31621310. .

  2. Wang, M, Safe, S, Hearon, SE, Phillips, TD. Strong adsorption of Polychlorinated Biphenyls by processed montmorillonite clays: Potential applications as toxin enterosorbents during disasters and floods. Environ. Pollut. 2019;255 (Pt 1):113210.
    doi: 10.1016/j.envpol.2019.113210. PubMed PMID:31542671. .

  3. Hedrick, E, Mohankumar, K, Lacey, A, Safe, S. Inhibition of NR4A1 Promotes ROS Accumulation and IL24-Dependent Growth Arrest in Rhabdomyosarcoma. Mol. Cancer Res. 2019;17 (11):2221-2232.
    doi: 10.1158/1541-7786.MCR-19-0408. PubMed PMID:31462501. PubMed Central PMC6825581.

  4. Safe, S, Han, H, Goldsby, J, Mohankumar, K, Chapkin, RS. Aryl Hydrocarbon Receptor (AhR) Ligands as Selective AhR Modulators: Genomic Studies. Curr Opin Toxicol. ;11-12 :10-20.
    doi: 10.1016/j.cotox.2018.11.005. PubMed PMID:31453421. PubMed Central PMC6709982.

  5. Jin, UH, Karki, K, Cheng, Y, Michelhaugh, SK, Mittal, S, Safe, S et al.. The aryl hydrocarbon receptor is a tumor suppressor-like gene in glioblastoma. J. Biol. Chem. 2019;294 (29):11342-11353.
    doi: 10.1074/jbc.RA119.008882. PubMed PMID:31171720. PubMed Central PMC6643041.

  6. Hedrick, E, Li, X, Cheng, Y, Lacey, A, Mohankumar, K, Zarei, M et al.. Potent inhibition of breast cancer by bis-indole-derived nuclear receptor 4A1 (NR4A1) antagonists. Breast Cancer Res. Treat. 2019;177 (1):29-40.
    doi: 10.1007/s10549-019-05279-9. PubMed PMID:31119568. PubMed Central PMC6681651.

  7. Li, X, Tjalkens, RB, Shrestha, R, Safe, S. Structure-dependent activation of gene expression by bis-indole and quinoline-derived activators of nuclear receptor 4A2. Chem Biol Drug Des. 2019;94 (4):1711-1720.
    doi: 10.1111/cbdd.13564. PubMed PMID:31102570. PubMed Central PMC6791730.

  8. Mohankumar, K, Li, X, Sridharan, S, Karki, K, Safe, S. Nuclear receptor 4A1 (NR4A1) antagonists induce ROS-dependent inhibition of mTOR signaling in endometrial cancer. Gynecol. Oncol. 2019;154 (1):218-227.
    doi: 10.1016/j.ygyno.2019.04.678. PubMed PMID:31053403. PubMed Central PMC6625344.

  9. Yoon, K, Chen, CC, Orr, AA, Barreto, PN, Tamamis, P, Safe, S et al.. Activation of COUP-TFI by a Novel Diindolylmethane Derivative. Cells. 2019;8 (3):.
    doi: 10.3390/cells8030220. PubMed PMID:30866413. PubMed Central PMC6468570.

  10. Kasiappan, R, Jutooru, I, Mohankumar, K, Karki, K, Lacey, A, Safe, S et al.. Reactive Oxygen Species (ROS)-Inducing Triterpenoid Inhibits Rhabdomyosarcoma Cell and Tumor Growth through Targeting Sp Transcription Factors. Mol. Cancer Res. 2019;17 (3):794-805.
    doi: 10.1158/1541-7786.MCR-18-1071. PubMed PMID:30610105. PubMed Central PMC6397684.

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