Scholars@Duke

• Background
• 

  Education, Training, & Certifications

  • Ph.D., National University of Ireland (Ireland) 1998
• 

  Duke Appointment History

  • Assistant Research Professor in Pharmacology & Cancer Biology, Pharmacology & Cancer Biology, Basic Science Departments 1999 - 2012
• Research
• 

  Selected Grants

  • Identification of Novel Targets in Treatment Resistant Prostate Cancer 2017 - 2022
  • Cancer cell intrinsic and extrinsic actions of steroid hormones in breast tumors awarded by Department of Defense 2018 - 2022
  • Development of mechanistically distinct androgen receptor antagonists and degraders for the treatment of advanced castra awarded by Department of Defense 2015 - 2019
  • Evaluation of G1 antiestrogens in models of estrogen action 2018 - 2019
  • Evaluation of G1T48 in models of estrogen action 2017 - 2018
  • Optimization of ERalpa-LBD-based CAR-T switch 2017 - 2018
  • Evaluation of the SERD XR5-28 in models of estrogen action 2016 - 2017
  • Evaluation of the therapeutic potential of combining VT464 and G1T38 in treatment-resistant prostate and breast cancer models 2016 - 2017
  • Targeting the CDK 4/6 axis in Castration Resistant Prostate Cancer 2015 - 2016
  • Evaluation of VT-464 in AR positive and ER positive breast cancer models 2015 - 2016
  • Determination of the antiandrogenic properties of VT-464, a novel CYP17 lyase inhibitor 2014 - 2015
  • Molecular Determinants of Androgen Receptor Pharmacology awarded by National Institutes of Health 2003 - 2013
  • Integrated instrument systems for maintenance and delivery of RNAi libraries awarded by National Institutes of Health 2008 - 2009
• 

  Industry Relationships

  • Celgene Corporation
  • G1 Therapeutics
  • GTx, Inc.
• Publications & Artistic Works
• 

  Selected Publications

  • Academic Articles

    • Johng, Dorhyun, Gonzalo Torga, Charles M. Ewing, Kideok Jin, John D. Norris, Donald P. McDonnell, and William B. Isaacs. “HOXB13 interaction with MEIS1 modifies proliferation and gene expression in prostate cancer..” Prostate 79, no. 4 (March 2019): 414–24. https://doi.org/10.1002/pros.23747.
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    • Wardell, Suzanne E., John D. Norris, and Donald P. McDonnell. “Targeting mutant estrogen receptors..” Elife 8 (January 16, 2019). https://doi.org/10.7554/eLife.44181.
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    • Tria, George S., Tinya Abrams, Jason Baird, Heather E. Burks, Brant Firestone, L Alex Gaither, Lawrence G. Hamann, et al. “Discovery of LSZ102, a Potent, Orally Bioavailable Selective Estrogen Receptor Degrader (SERD) for the Treatment of Estrogen Receptor Positive Breast Cancer..” J Med Chem 61, no. 7 (April 12, 2018): 2837–64. https://doi.org/10.1021/acs.jmedchem.7b01682.
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    • McDonnell, Donald P., John D. Norris, and Ching-Yi Chang. “Neomorphic ERα Mutations Drive Progression in Breast Cancer and Present a Challenge for New Drug Discovery..” Cancer Cell 33, no. 2 (February 12, 2018): 153–55. https://doi.org/10.1016/j.ccell.2018.01.014.
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    • Norris, John D., Stephanie J. Ellison, Jennifer G. Baker, David B. Stagg, Suzanne E. Wardell, Sunghee Park, Holly M. Alley, et al. “Androgen receptor antagonism drives cytochrome P450 17A1 inhibitor efficacy in prostate cancer..” J Clin Invest 127, no. 6 (June 1, 2017): 2326–38. https://doi.org/10.1172/JCI87328.
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    • Stice, James P., Suzanne E. Wardell, John D. Norris, Alexander P. Yllanes, Holly M. Alley, Victoria O. Haney, Hannah S. White, et al. “CDK4/6 Therapeutic Intervention and Viable Alternative to Taxanes in CRPC..” Mol Cancer Res 15, no. 6 (June 2017): 660–69. https://doi.org/10.1158/1541-7786.MCR-17-0028.
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    • Burks, Heather E., Tinya Abrams, Christina A. Kirby, Jason Baird, Alexander Fekete, Lawrence G. Hamann, Sunkyu Kim, et al. “Discovery of an Acrylic Acid Based Tetrahydroisoquinoline as an Orally Bioavailable Selective Estrogen Receptor Degrader for ERα+ Breast Cancer..” J Med Chem 60, no. 7 (April 13, 2017): 2790–2818. https://doi.org/10.1021/acs.jmedchem.6b01468.
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    • Christenson, Jessica L., Kiel T. Butterfield, Nicole S. Spoelstra, John D. Norris, Jatinder S. Josan, Julie A. Pollock, Donald P. McDonnell, Benita S. Katzenellenbogen, John A. Katzenellenbogen, and Jennifer K. Richer. “MMTV-PyMT and Derived Met-1 Mouse Mammary Tumor Cells as Models for Studying the Role of the Androgen Receptor in Triple-Negative Breast Cancer Progression..” Horm Cancer 8, no. 2 (April 2017): 69–77. https://doi.org/10.1007/s12672-017-0285-6.
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    • Pollock, Julie A., Suzanne E. Wardell, Alexander A. Parent, David B. Stagg, Stephanie J. Ellison, Holly M. Alley, Christina A. Chao, et al. “Inhibiting androgen receptor nuclear entry in castration-resistant prostate cancer..” Nat Chem Biol 12, no. 10 (October 2016): 795–801. https://doi.org/10.1038/nchembio.2131.
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    • Wardell, Suzanne E., Matthew J. Ellis, Holly M. Alley, Koleen Eisele, Todd VanArsdale, Stephen G. Dann, Kim T. Arndt, et al. “Efficacy of SERD/SERM Hybrid-CDK4/6 Inhibitor Combinations in Models of Endocrine Therapy-Resistant Breast Cancer..” Clin Cancer Res 21, no. 22 (November 15, 2015): 5121–30. https://doi.org/10.1158/1078-0432.CCR-15-0360.
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    • Gustafson, Jeffrey L., Taavi K. Neklesa, Carly S. Cox, Anke G. Roth, Dennis L. Buckley, Hyun Seop Tae, Thomas B. Sundberg, et al. “Small-Molecule-Mediated Degradation of the Androgen Receptor through Hydrophobic Tagging..” Angew Chem Int Ed Engl 54, no. 33 (August 10, 2015): 9659–62. https://doi.org/10.1002/anie.201503720.
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    • McDonnell, Donald P., Suzanne E. Wardell, and John D. Norris. “Oral Selective Estrogen Receptor Downregulators (SERDs), a Breakthrough Endocrine Therapy for Breast Cancer..” J Med Chem 58, no. 12 (June 25, 2015): 4883–87. https://doi.org/10.1021/acs.jmedchem.5b00760.
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    • McDonnell, Donald P., Sunghee Park, Matthew T. Goulet, Jeff Jasper, Suzanne E. Wardell, Ching-Yi Chang, John D. Norris, John R. Guyton, and Erik R. Nelson. “Obesity, cholesterol metabolism, and breast cancer pathogenesis..” Cancer Res 74, no. 18 (September 15, 2014): 4976–82. https://doi.org/10.1158/0008-5472.CAN-14-1756.
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    • Shatnawi, A., J. D. Norris, C. Chaveroux, J. S. Jasper, A. B. Sherk, D. P. McDonnell, and V. Giguère. “ELF3 is a repressor of androgen receptor action in prostate cancer cells..” Oncogene 33, no. 7 (February 13, 2014): 862–71. https://doi.org/10.1038/onc.2013.15.
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    • Teng, Christina, Bonnie Goodwin, Keith Shockley, Menghang Xia, Ruili Huang, John Norris, B Alex Merrick, Anton M. Jetten, Christopher P. Austin, and Raymond R. Tice. “Bisphenol A affects androgen receptor function via multiple mechanisms..” Chem Biol Interact 203, no. 3 (May 25, 2013): 556–64. https://doi.org/10.1016/j.cbi.2013.03.013.
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    • Norris, John D., Ching-Yi Chang, Bryan M. Wittmann, Rebecca S. Kunder, Huaxia Cui, Daju Fan, James D. Joseph, and Donald P. McDonnell. “The homeodomain protein HOXB13 regulates the cellular response to androgens..” Molecular Cell 36, no. 3 (November 2009): 405–16. https://doi.org/10.1016/j.molcel.2009.10.020.
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    • Frigo, Daniel E., Andrea B. Sherk, Bryan M. Wittmann, John D. Norris, Qianben Wang, James D. Joseph, Aidan P. Toner, Myles Brown, and Donald P. McDonnell. “Induction of Kruppel-like factor 5 expression by androgens results in increased CXCR4-dependent migration of prostate cancer cells in vitro..” Mol Endocrinol 23, no. 9 (September 2009): 1385–96. https://doi.org/10.1210/me.2009-0010.
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    • Joseph, James D., Bryan M. Wittmann, Mary A. Dwyer, Huaxia Cui, Delita A. Dye, Donald P. McDonnell, and John D. Norris. “Inhibition of prostate cancer cell growth by second-site androgen receptor antagonists..” Proc Natl Acad Sci U S A 106, no. 29 (July 21, 2009): 12178–83. https://doi.org/10.1073/pnas.0900185106.
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    • Norris, John David, James David Joseph, Andrea Barreto Sherk, Dalia Juzumiene, Philip Stewart Turnbull, Stephen William Rafferty, Huaxia Cui, et al. “Differential presentation of protein interaction surfaces on the androgen receptor defines the pharmacological actions of bound ligands..” Chemistry & Biology 16, no. 4 (April 2009): 452–60. https://doi.org/10.1016/j.chembiol.2009.01.016.
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    • Sherk, Andrea B., Daniel E. Frigo, Christine G. Schnackenberg, Jeffrey D. Bray, Nicholas J. Laping, Walter Trizna, Marlys Hammond, et al. “Development of a small-molecule serum- and glucocorticoid-regulated kinase-1 antagonist and its evaluation as a prostate cancer therapeutic..” Cancer Res 68, no. 18 (September 15, 2008): 7475–83. https://doi.org/10.1158/0008-5472.CAN-08-1047.
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    • Kazmin, Dmitri, Tatiana Prytkova, C Edgar Cook, Russell Wolfinger, Tzu-Ming Chu, David Beratan, J. D. Norris, Ching-yi Chang, and Donald P. McDonnell. “Linking ligand-induced alterations in androgen receptor structure to differential gene expression: a first step in the rational design of selective androgen receptor modulators..” Mol Endocrinol 20, no. 6 (June 2006): 1201–17. https://doi.org/10.1210/me.2005-0309.
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    • Wu, Ya-Ling, Xiaojing Yang, Zhong Ren, Donald P. McDonnell, John D. Norris, Timothy M. Willson, and Geoffrey L. Greene. “Structural basis for an unexpected mode of SERM-mediated ER antagonism..” Mol Cell 18, no. 4 (May 13, 2005): 413–24. https://doi.org/10.1016/j.molcel.2005.04.014.
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    • Juzumiene, Dalia, Ching-yi Chang, Daju Fan, Tanya Hartney, John D. Norris, and Donald P. McDonnell. “Single-step purification of full-length human androgen receptor..” Nucl Recept Signal 3 (2005). https://doi.org/10.1621/nrs.03001.
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    • Chang, Ching-yi, John D. Norris, Michelle Jansen, Huey-Jing Huang, and Donald P. McDonnell. “Application of random peptide phage display to the study of nuclear hormone receptors..” Methods Enzymol 364 (2003): 118–42. https://doi.org/10.1016/s0076-6879(03)64007-3.
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    • Huang, Huey-Jing, John D. Norris, and Donald P. McDonnell. “Identification of a negative regulatory surface within estrogen receptor alpha provides evidence in support of a role for corepressors in regulating cellular responses to agonists and antagonists..” Mol Endocrinol 16, no. 8 (August 2002): 1778–92. https://doi.org/10.1210/me.2002-0089.
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    • McDonnell, Donald P., Ashini Wijayaratne, Ching-yi Chang, and John D. Norris. “Elucidation of the molecular mechanism of action of selective estrogen receptor modulators..” Am J Cardiol 90, no. 1A (July 3, 2002): 35F-43F. https://doi.org/10.1016/s0002-9149(01)02221-4.
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    • McDonnell, Donald P., and John D. Norris. “Connections and regulation of the human estrogen receptor..” Science 296, no. 5573 (May 31, 2002): 1642–44. https://doi.org/10.1126/science.1071884.
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    • Norris, John D., Daju Fan, Andrea Sherk, and Donald P. McDonnell. “A negative coregulator for the human ER..” Mol Endocrinol 16, no. 3 (March 2002): 459–68. https://doi.org/10.1210/mend.16.3.0787.
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    • McDonnell, Donald P., Caroline E. Connor, Ashini Wijayaratne, Ching-Yi Chang, and John D. Norris. “Definition of the molecular and cellular mechanisms underlying the tissue-selective agonist/antagonist activities of selective estrogen receptor modulators..” Recent Prog Horm Res 57 (2002): 295–316.
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    • McDonnell, D. P., C. Y. Chang, and J. D. Norris. “Capitalizing on the complexities of estrogen receptor pharmacology in the quest for the perfect SERM..” Ann N Y Acad Sci 949 (December 2001): 16–35. https://doi.org/10.1111/j.1749-6632.2001.tb03999.x.
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    • McDonnell, D. P., C. E. Connor, J. Hall, C. Y. Chang, M. S. Jansen, and J. D. Norris. “The molecular pharmacology of estrogen receptor agonists, antagonists and SERMs.” Bone 28, no. 5 (May 1, 2001): S68–S68.
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    • Connor, C. E., J. D. Norris, G. Broadwater, T. M. Willson, M. M. Gottardis, M. W. Dewhirst, and D. P. McDonnell. “Circumventing tamoxifen resistance in breast cancers using antiestrogens that induce unique conformational changes in the estrogen receptor..” Cancer Res 61, no. 7 (April 1, 2001): 2917–22.
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    • Norris, J. D., C. Chang, and D. P. McDonnell. “Estrogen receptor-cofactor interactions as targets for novel drug discovery..” Ernst Schering Research Foundation Workshop, no. 34 (January 2001): 181–201.
    • McDonnell, D. P., C. Y. Chang, and J. D. Norris. “Development of peptide antagonists that target estrogen receptor-cofactor interactions..” J Steroid Biochem Mol Biol 74, no. 5 (November 30, 2000): 327–35. https://doi.org/10.1016/s0960-0760(00)00109-6.
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    • Tcherepanova, I., P. Puigserver, J. D. Norris, B. M. Spiegelman, and D. P. McDonnell. “Modulation of estrogen receptor-alpha transcriptional activity by the coactivator PGC-1..” J Biol Chem 275, no. 21 (May 26, 2000): 16302–8. https://doi.org/10.1074/jbc.M001364200.
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    • Chang, C. Y., J. D. Norris, H. Grøn, L. A. Paige, P. T. Hamilton, D. J. Kenan, D. Fowlkes, and D. P. McDonnell. “Dissection of the LXXLL nuclear receptor-coactivator interaction motif using combinatorial peptide libraries: discovery of peptide antagonists of estrogen receptors alpha and beta..” Mol Cell Biol 19, no. 12 (December 1999): 8226–39. https://doi.org/10.1128/mcb.19.12.8226.
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    • Wijayaratne, A. L., S. C. Nagel, L. A. Paige, D. J. Christensen, J. D. Norris, D. M. Fowlkes, and D. P. McDonnell. “Comparative analyses of mechanistic differences among antiestrogens..” Endocrinology 140, no. 12 (December 1999): 5828–40. https://doi.org/10.1210/endo.140.12.7164.
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    • Wijayaratne, Ashini L., Susan C. Nagel, Lisa A. Paige, Dale J. Christensen, John D. Norris, Dana M. Fowlkes, and Donald P. McDonnell. “Comparative Analyses of Mechanistic Differences Among Antiestrogens1..” Endocrinology 140, no. 12 (December 1, 1999): 5828–40. https://doi.org/10.1210/endo.140.12.7164.
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    • Norris, J. D., L. A. Paige, D. J. Christensen, C. Y. Chang, M. R. Huacani, D. Fan, P. T. Hamilton, D. M. Fowlkes, and D. P. McDonnell. “Peptide antagonists of the human estrogen receptor..” Science 285, no. 5428 (July 30, 1999): 744–46. https://doi.org/10.1126/science.285.5428.744.
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    • Paige, L. A., D. J. Christensen, H. Grøn, J. D. Norris, E. B. Gottlin, K. M. Padilla, C. Y. Chang, et al. “Estrogen receptor (ER) modulators each induce distinct conformational changes in ER alpha and ER beta..” Proc Natl Acad Sci U S A 96, no. 7 (March 30, 1999): 3999–4004. https://doi.org/10.1073/pnas.96.7.3999.
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    • Ramamoorthy, K., F. Wang, I. C. Chen, S. Safe, J. D. Norris, D. P. McDonnell, K. W. Gaido, et al. “Potency of combined estrogenic pesticides: Synergy between synthetic oestrogens?.” Chemtracts 11, no. 4 (April 1, 1998): 306–8.
    • Norris, J. D., D. Fan, M. R. Stallcup, and D. P. McDonnell. “Enhancement of estrogen receptor transcriptional activity by the coactivator GRIP-1 highlights the role of activation function 2 in determining estrogen receptor pharmacology..” J Biol Chem 273, no. 12 (March 20, 1998): 6679–88. https://doi.org/10.1074/jbc.273.12.6679.
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    • Wagner, B. L., J. D. Norris, T. A. Knotts, N. L. Weigel, and D. P. McDonnell. “The nuclear corepressors NCoR and SMRT are key regulators of both ligand- and 8-bromo-cyclic AMP-dependent transcriptional activity of the human progesterone receptor..” Mol Cell Biol 18, no. 3 (March 1998): 1369–78. https://doi.org/10.1128/mcb.18.3.1369.
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    • Willson, T. M., J. D. Norris, B. L. Wagner, I. Asplin, P. Baer, H. R. Brown, S. A. Jones, et al. “Dissection of the molecular mechanism of action of GW5638, a novel estrogen receptor ligand, provides insights into the role of estrogen receptor in bone..” Endocrinology 138, no. 9 (September 1997): 3901–11. https://doi.org/10.1210/endo.138.9.5358.
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    • Norris, J. D., D. Fan, S. A. Kerner, and D. P. McDonnell. “Identification of a third autonomous activation domain within the human estrogen receptor..” Mol Endocrinol 11, no. 6 (June 1997): 747–54. https://doi.org/10.1210/mend.11.6.0008.
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    • Ramamoorthy, K., F. Wang, I. C. Chen, J. D. Norris, D. P. McDonnell, L. S. Leonard, K. W. Gaido, W. P. Bocchinfuso, K. S. Korach, and S. Safe. “Estrogenic activity of a dieldrin/toxaphene mixture in the mouse uterus, MCF-7 human breast cancer cells, and yeast-based estrogen receptor assays: no apparent synergism..” Endocrinology 138, no. 4 (April 1997): 1520–27. https://doi.org/10.1210/endo.138.4.5056.
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    • Ramamoorthy, K., F. Wang, I. C. Chen, S. Safe, J. D. Norris, D. P. McDonnell, K. W. Gaido, W. P. Bocchinfuso, and K. S. Korach. “Potency of combined estrogenic pesticides..” Science 275, no. 5298 (January 17, 1997): 405–6. https://doi.org/10.1126/science.275.5298.405.
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    • Marks, J. R., G. Huper, J. P. Vaughn, P. L. Davis, J. Norris, D. P. McDonnell, R. W. Wiseman, P. A. Futreal, and J. D. Iglehart. “BRCA1 expression is not directly responsive to estrogen..” Oncogene 14, no. 1 (January 9, 1997): 115–21. https://doi.org/10.1038/sj.onc.1200808.
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    • McDonnell, D. P., and J. D. Norris. “Analysis of the molecular pharmacology of estrogen receptor agonists and antagonists provides insights into the mechanism of action of estrogen in bone..” Osteoporos Int 7 Suppl 1 (1997): S29–34.
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    • Norris, J., D. Fan, and D. P. McDonnell. “Erratum: Identification of the sequences within the human coplement 3 promoter required for estrogen responsiveness provides insight into the mechanism of tamoxifen mixed agonist activity (Molecular Endocrinology (1996) 10 (1605-1616)).” Molecular Endocrinology 11, no. 3 (January 1, 1997).
    • Fan, J. D., B. L. Wagner, and D. P. McDonnell. “Identification of the sequences within the human complement 3 promoter required for estrogen responsiveness provides insight into the mechanism of tamoxifen mixed agonist activity..” Mol Endocrinol 10, no. 12 (December 1996): 1605–16. https://doi.org/10.1210/mend.10.12.8961270.
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    • Petranka, J., J. Zhao, J. Norris, N. B. Tweedy, R. E. Ware, P. J. Sims, and W. F. Rosse. “Structure-function relationships of the complement regulatory protein, CD59..” Blood Cells Mol Dis 22, no. 3 (1996): 281–96. https://doi.org/10.1006/bcmd.1996.0111.
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    • Norris, J., D. Fan, C. Aleman, J. R. Marks, P. A. Futreal, R. W. Wiseman, J. D. Iglehart, P. L. Deininger, and D. P. McDonnell. “Identification of a new subclass of Alu DNA repeats which can function as estrogen receptor-dependent transcriptional enhancers..” J Biol Chem 270, no. 39 (September 29, 1995): 22777–82. https://doi.org/10.1074/jbc.270.39.22777.
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    • Norris, J., S. Hall, R. E. Ware, T. Kamitani, H. M. Chang, E. Yeh, and W. F. Rosse. “Glycosyl-phosphatidylinositol anchor synthesis in paroxysmal nocturnal hemoglobinuria: partial or complete defect in an early step..” Blood 83, no. 3 (February 1, 1994): 816–21.
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  • Conference Papers

    • Ellison, S. J., J. D. Norris, S. Wardell, J. R. Eisner, W. J. Hoekstra, D. B. Stagg, H. M. Alley, W. R. Moore, and D. P. McDonnell. “Abstract P3-14-04: Effects of the dual selective CYP17 lyase inhibitor and androgen receptor (AR) antagonist, VT-464, on AR+ and ER+ tumor models in vitro and in vivo.” In Poster Session Abstracts. American Association for Cancer Research, 2016. https://doi.org/10.1158/1538-7445.sabcs15-p3-14-04.
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    • Moore, William R., John D. Norris, Suzanne Wardell, Joel Robert Eisner, William J. Hoekstra, Robert J. Schotzinger, and Donald P. McDonnell. “Direct effects of the selective CYP17 lyase (L) inhibitor, VT-464, on the androgen receptor (AR) and its oral activity in an F876L tumor mouse xenograft model..” In Journal of Clinical Oncology, 33:263–263. American Society of Clinical Oncology (ASCO), 2015. https://doi.org/10.1200/jco.2015.33.7_suppl.263.
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    • Katzenellenbogen, John A., Julie A. Pollock, Alexander A. Parent, Suzanne Elizabeth Wardell, Donald P. McDonnell, and John D. Norris. “Structurally Novel Antagonists of Androgen Receptors with Elevated Potency for Antiandrogen-Resistant Receptor Mutants in Prostate Cancer: Tetra-Aryl-Substituted Cyclobutanes.” In Endocrine Reviews, Vol. 35. ENDOCRINE SOC, 2014.
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    • Katzenellenbogen, John A., Julie A. Pollock, Alexander A. Parent, Suzanne Elizabeth Wardell, Donald P. McDonnell, and John D. Norris. “Structurally Novel Antagonists of Androgen Receptors with Elevated Potency for Antiandrogen-Resistant Receptor Mutants in Prostate Cancer: Tetra-Aryl-Substituted Cyclobutanes.” In Endocrine Reviews, Vol. 35. ENDOCRINE SOC, 2014.
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