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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. 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; :.
    doi: 10.1007/s10549-019-05279-9. PubMed PMID:31119568. .

  2. 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; :.
    doi: 10.1111/cbdd.13564. PubMed PMID:31102570. .

  3. 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; :.
    doi: 10.1016/j.ygyno.2019.04.678. PubMed PMID:31053403. .

  4. 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.

  5. 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.

  6. 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). 2019;43 (5):952-962.
    doi: 10.1038/s41366-018-0276-x. PubMed PMID:30538281. .

  7. 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. .

  8. 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.

  9. 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.

  10. 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.

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