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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. Mohankumar, K, Li, X, Sung, N, Cho, YJ, Han, SJ, Safe, S et al.. Bis-Indole-Derived Nuclear Receptor 4A1 (NR4A1, Nur77) Ligands as Inhibitors of Endometriosis. Endocrinology. 2020;161 (4):.
    doi: 10.1210/endocr/bqaa027. PubMed PMID:32099996. PubMed Central PMC7105386.

  2. Kumaravel, S, Singh, S, Roy, S, Venkatasamy, L, White, TK, Sinha, S et al.. CXCL11-CXCR3 Axis Mediates Tumor Lymphatic Cross Talk and Inflammation-Induced Tumor, Promoting Pathways in Head and Neck Cancers. Am. J. Pathol. 2020;190 (4):900-915.
    doi: 10.1016/j.ajpath.2019.12.004. PubMed PMID:32035061. PubMed Central PMC7180517.

  3. Nottingham, E, Sekar, V, Mondal, A, Safe, S, Rishi, AK, Singh, M et al.. The Role of Self-Nanoemulsifying Drug Delivery Systems of CDODA-Me in Sensitizing Erlotinib-Resistant Non-Small Cell Lung Cancer. J Pharm Sci. 2020;109 (6):1867-1882.
    doi: 10.1016/j.xphs.2020.01.010. PubMed PMID:31954111. .

  4. Karki, K, Wright, GA, Mohankumar, K, Jin, UH, Zhang, XH, Safe, S et al.. A Bis-Indole-Derived NR4A1 Antagonist Induces PD-L1 Degradation and Enhances Antitumor Immunity. Cancer Res. 2020;80 (5):1011-1023.
    doi: 10.1158/0008-5472.CAN-19-2314. PubMed PMID:31911554. PubMed Central PMC7056589.

  5. Garcia-Villatoro, EL, DeLuca, JAA, Callaway, ES, Allred, KF, Davidson, LA, Hensel, ME et al.. Effects of high-fat diet and intestinal aryl hydrocarbon receptor deletion on colon carcinogenesis. Am. J. Physiol. Gastrointest. Liver Physiol. 2020;318 (3):G451-G463.
    doi: 10.1152/ajpgi.00268.2019. PubMed PMID:31905023. PubMed Central PMC7137094.

  6. Karki, K, Li, X, Jin, UH, Mohankumar, K, Zarei, M, Michelhaugh, SK et al.. Nuclear receptor 4A2 (NR4A2) is a druggable target for glioblastomas. J. Neurooncol. 2020;146 (1):25-39.
    doi: 10.1007/s11060-019-03349-y. PubMed PMID:31754919. PubMed Central PMC7054911.

  7. Chatterjee, S, Walsh, EN, Yan, AL, Giese, KP, Safe, S, Abel, T et al.. Pharmacological activation of Nr4a rescues age-associated memory decline. Neurobiol. Aging. 2020;85 :140-144.
    doi: 10.1016/j.neurobiolaging.2019.10.001. PubMed PMID:31732218. PubMed Central PMC6917472.

  8. 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;32 (11):2353-2364.
    doi: 10.1021/acs.chemrestox.9b00352. PubMed PMID:31621310. PubMed Central PMC6938648.

  9. 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. PubMed Central PMC6878994.

  10. 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.

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