Elizabeth Wilson, PhD

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 testosterone and dihydrotestosterone. Our focus is understanding molecular mechanisms of androgen receptor action. We use a variety of techniques to establish structure-function relationships in the ligand binding, DNA binding and transcriptional activation domains of the receptor. Specific naturally occurring mutations in the androgen receptor gene cause the androgen insensitivity syndrome that help in studies on receptor domain activity. Coactivator and corepressor proteins are being identified and characterized which interact with the receptor to modulate gene expression. We are determining mechanisms for androgen receptor reactivation in castration-recurrent prostate cancer

REPRESENTATIVE PUBLICATIONS

  • James SR, Cedeno CD, Sharma A, Zhang W, Mohler JL, Odunsi K, Wilson EM, Karpf AR 2013 DNA methylation and nucleosome occupancy regulate the cancer germline antigen gene MAGEA11. Epigenetics 8:849-863
  • Su S, Minges JT, Grossman G, Blackwelder AJ, Mohler JL, Wilson EM 2013 Proto-oncogene activity of melanoma antigen-A11 (MAGE-A11) regulates retinoblastoma-related p107 and E2F1. J Biol Chem 288:24809-24824
  • Minges JT, Su S, Grossman G, Blackwelder AJ, Pop EA, Mohler JL, Wilson EM 2013 Melanoma antigen-A11 (MAGE-A11) enhances transcriptional activity by linking androgen receptor dimers. J Biol Chem 288:1939-1952
  • Askew EB, Minges JT, Hnat AT, Wilson EM 2012 Structural features discriminate androgen receptor N/C terminal and coactivator interactions. Mol Cell Endo 348:403-410
  • Titus MA, Zeithaml B, Kantor B, Li X, Haack K, Moore DT, Wilson EM, Mohler JL, Kafri T 2012 Dominant-negative androgen receptor inhibition of intracrine androgen-dependent growth of castration-recurrent prostate cancer. PLoS One 7:e30192
  • Lagarde WH, Blackwelder AJ, Minges JT, Hnat AT, French FS, Wilson EM 2012 Androgen receptor exon 1 mutation causes androgen insensitivity by creating a phosphorylation site and inhibiting MAGE-A11 activation of NH2- and carboxyl-terminal interaction-dependent transactivation. J Biol Chem 287:10905-10915
  • Aninye IO, Berg KC, Mollo AR, Nordeen SK, Wilson EM, Shapiro DJ 2012 8-Alkylthio-6-thio-substituted theophylline analogues as selective noncompetitive progesterone receptor antagonists. Steroids 77:596-601
  • Cherian MT, Wilson EM, Shapiro DJ 2012 A competitive inhibitor that reduces recruitment of androgen receptor to androgen-responsive genes. J Biol Chem 287:23368-23380
  • Su S, Blackwelder AJ, Grossman G, Minges JT, Yuan L, Young SL, Wilson EM 2012 Primate-specific melanoma antigen-A11 regulates isoform-specific human progesterone receptor-B transactivation. J Biol Chem 287:34809-34824
  • Mohler JL, Titus MA, Bai S, Kennerley BJ, Lih FB, Tomer KB, Wilson EM 2011 Activation of the androgen receptor by intratumoral bioconversion of androstanediol to dihydrotestosterone in prostate cancer. Cancer Res71:1486-1496
  • Liu Q, Su S, Blackwelder AJ, Minges JT, Wilson EM 2011 Gain in transcriptional activity by primate-specific coevolution of melanoma antigen-A11 and its interaction site in the androgen receptor.J Biol Chem 286:29951-29963
  • Mohler JL, Titus MA, Wilson EM 2011 Potential prostate cancer drug target: bioactivation of androstanediol by conversion to dihydrotestosterone. Clin Can Res 17:5844-5849
  • Kretzer NM, Cherian MT, Mao C, Aninye IO, Reynolds PD, Schiff R, Hergenrother PJ, Nordeen SK, Wilson EM, Shapiro DJ 2010 A noncompetitive small molecule inhibitor of estrogen-regulated gene expression and breast cancer cell growth that enhances proteasome-dependent degradation of estrogen receptor alpha. J Biol Chem 285:41863-41873
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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

    CONTACT INFO

    3201 MBRB
    Campus Box # 7500
    Chapel Hill, NC 27599

    Office: 919-966-5168

    emw@med.unc.edu