Elizabeth Wilson, PhD

HONORS & AWARDS

RESEARCH

Summary:

Androgen Regulation of Gene Expression

Steroid hormone receptors are ligand activated transcription factors that regulate gene expression by binding specific DNA sequences and interacting with other transcriptional regulatory proteins. We study the androgen receptor, the steroid receptor that mediates the biological effects of the androgens testosterone and dihydrotestosterone. Our focus is to elucidate the molecular mechanisms of androgen receptor action. We use a variety of techniques to establish structure-function relationships of the ligand binding, DNA binding and transcriptional activation domains of the receptor. Specific naturally occurring mutations in the androgen receptor gene that cause androgen insensitivity are utilized in studies on receptor domain activity. Coactivator and corepressor proteins are being identified and characterized which interact with the receptor to modulate gene expression. Collaborative studies are underway to crystallize the purified full-length androgen receptor bound to androgen and DNA. In addition, we are investigating certain environmental chemicals with androgen or antiandrogen activity that act as endocrine disruptors to influence human sexual development or behavior.

REPRESENTATIVE PUBLICATIONS

    • He B, Gampe RT, Hnat AT, Faggart JL, Minges JT, French FS, Wilson EM 2006 Probing the functional link between androgen receptor coactivator and ligand binding sites in prostate cancer and androgen insensitivity. J Biol Chem 281:6648-6663
    • Lu NZ, Wardell SE, Burnstein KL, Defranco D, Fuller PJ, Giguere V, Hochberg RB, McKay L, Renoir JM, Weigel NL, Wilson EM, McDonnell DP, Cidlowski JA. 2006 International Union of Pharmacology. LXV. The pharmacology and classification of the nuclear receptor superfamily: glucocorticoid, mineralocorticoid, progesterone, and androgen receptors. Pharmacol Rev 58:782-797
    • Wilson EM 2007 Muscle bound? A tissue-selective nonsteroidal androgen receptor modulator. Endocrinology 148:1-3
      Askew EB, Gampe RT, Stanley TB, Faggart JL, Wilson EM 2007 Modulation of androgen receptor activation function 2 by testosterone and dihydrotestosterone. J Biol Chem 282:25801-25816
    • Bai S, Wilson EM 2008 Epidermal growth factor-dependent phosphorylation and ubiquitinylation of MAGE-11 regulates its interaction with the androgen receptor. Mol Cell Biol 28:1947-1963
    • Bai S, Grossman G, Yuan L, Lessey BA, French FS, Young SL, Wilson EM 2008 Hormone control and expression of androgen receptor coregulator MAGE-11 in human endometrium during the window of receptivity to embryo implantation. Mol Hum Reproduction 14:107-116
    • Carson JD, Jenkins RL, Wilson EM, Howell WM, Moore R 2008 Naturally occurring progesterone in Loblolly pine (Pinus Taeda L.): a major steroid precursor of environmental androgens. Environ Tox Chem 27:1273-1278
    • Mao C, Patterson NM, Cherian MT, Aninye IO, Zhang C, Montoya JB, Cheng J, Putt KS, Hergenrother PJ, Wilson EM, Nardulli AM, Nordeen SK, Shapiro DJ 2008 A new small molecule inhibitor of estrogen receptor alpha binding to estrogen response elements blocks estrogen-dependent growth of cancer cells. J Biol Chem 283:12819-12830
    • Ponguta LA, Gregory CW, French FS, Wilson EM 2008 Site-specific androgen receptor serine phosphorylation linked to epidermal growth factor-dependent growth of castration-recurrent prostate cancer. J Biol Chem 283:20989-21001
    • Karpf AR, Bai S, James SR, Mohler JL, Wilson EM 2009 Increased expression of androgen receptor coregulator MAGE-11 in prostate cancer by DNA hypomethylation and cyclic AMP. Mol Cancer Res 7:523-535
    • Titus MA, Tan JA, Gregory CW, Ford OH, Subramanian RR, Fu H, Wilson EM, Mohler JL, French FS 2009 14-3-3h amplifies androgen receptor actions in prostate cancer. Clin Cancer Res 15:7571-7581
    • Askew EB, Bai S, Hnat AT, Minges JT, Wilson EM 2009 Melanoma antigen gene protein-A11 (MAGE-11) F-box links the androgen receptor NH2-terminal transactivation domain to p160 coactivators. J Biol Chem 284:34793-34808
    • Wilson EM 2009 Methods for measuring ligand dissociation and nuclear receptor turnover in whole cells. Methods Mol Biol, Chapter 2: The Nuclear Receptor Superfamily, IJ McEwan (ed), Humana Press, Inc. 505:21-33
    • Wilson EM 2009 Functional motifs of the androgen receptor. In: Androgen Action in Prostate Cancer. Tindall D, Mohler J (eds) Springer New York pp 241-267
    • Wilson EM 2010 Androgen receptor molecular biology and potential targets in prostate cancer. Therap Adv Urol 2:105-117
    • Askew EB, Bai S, Blackwelder AJ, Wilson EM 2010 Transcriptional synergy between melanoma antigen gene protein-A11 (MAGE-11) and p300 in androgen receptor signaling. J Biol Chem 285:21824-21836
    • Orr CR, Montie HL, Liu Y, Bolzoni E, Jenkins SC, Wilson EM, Joseph JD, McDonnell DP, Merry DE 2010 An intramolecular interaction of the androgen receptor is required for its aggregation and toxicity in spinal and bulbar muscular atrophy. J Biol Chem, Epub ahead of print
    • Hu S, Yao G, Guan X, Ni Z, Ma W, Wilson EM, French FS, Liu Q, Zhang Y 2010 Research resource: Genome-wide mapping of in vivo androgen receptor binding sites in mouse epididymis. Mol Endocrinol Epub ahead of print
    • Wilson EM 2010 Analysis of interdomain interactions of the androgen receptor. In: Methods in Molecular Biology: Androgen Action. Chapter 9, F Saatcioglu (ed), Humana Press, Inc., in press

      CONTACT INFO

      3340C MBRB
      Campus Box # 7500
      Chapel Hill, NC 27599

      Office: 919-966-5168

      emw@med.unc.edu