John David Norris | Scholars@Duke

John David Norris
Associate Research Professor in Pharmacology & Cancer Biology

Molecular pharmacology of the nucler receptor class of transcription factors. Special interest in the mode of action of tissue specific ligands for the estrogen and androgen receptors.

Current Appointments & Affiliations

Associate Research Professor in Pharmacology & Cancer Biology, Pharmacology & Cancer Biology, Basic Science Departments 2012

Contact Information

Duke Box 3813, Durham, NC 27710
Research Drive, LSRC Bldg, C251, Durham, NC 27710
norri003@duke.edu (919) 684-0233

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
- Cancer cell intrinsic and extrinsic actions of steroid hormones in breast tumors awarded by Department of Defense 2018 - 2022
- Identification of Novel Targets in Treatment Resistant Prostate Cancer awarded by Celgene Corporation 2017 - 2020
- Evaluation of G1 antiestrogens in models of estrogen action awarded by G1 Therapeutics Inc. 2018 - 2019
- Development of mechanistically distinct androgen receptor antagonists and degraders for the treatment of advanced castra awarded by Department of Defense 2015 - 2018
- Evaluation of G1T48 in models of estrogen action awarded by G1 Therapeutics Inc. 2017 - 2018
- Optimization of ERalpa-LBD-based CAR-T switch awarded by Cell Design Labs, Inc 2017 - 2018
- Evaluation of the SERD XR5-28 in models of estrogen action awarded by G1 Therapeutics Inc. 2016 - 2017
- Evaluation of the therapeutic potential of combining VT464 and G1T38 in treatment-resistant prostate and breast cancer models awarded by Innocrin Pharmaceutical, Inc. 2016 - 2017
- Targeting the CDK 4/6 axis in Castration Resistant Prostate Cancer awarded by G1 Therapeutics Inc. 2015 - 2016
- Evaluation of VT-464 in AR positive and ER positive breast cancer models awarded by Innocrin Pharmaceutical, Inc. 2015 - 2016
- Determination of the antiandrogenic properties of VT-464, a novel CYP17 lyase inhibitor awarded by Viamet Pharmaceuticals 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
Publications & Artistic Works
Selected Publications
- Conference Papers
  - Ellison, S, Norris, J, Wardell, S, Eisner, J, Hoekstra, W, Stagg, D, Alley, H, Moore, W, and McDonnell, D. "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." February 15, 2016. Full Text
  - Moore, WR, Norris, JD, Wardell, S, Eisner, JR, Hoekstra, WJ, Schotzinger, RJ, and McDonnell, DP. "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." March 2015. Full Text
  - Katzenellenbogen, JA, Pollock, JA, Parent, AA, Wardell, SE, McDonnell, DP, and Norris, JD. "Structurally Novel Antagonists of Androgen Receptors with Elevated Potency for Antiandrogen-Resistant Receptor Mutants in Prostate Cancer: Tetra-Aryl-Substituted Cyclobutanes." June 2014. Link to Item
  - Katzenellenbogen, JA, Pollock, JA, Parent, AA, Wardell, SE, McDonnell, DP, and Norris, JD. "Structurally Novel Antagonists of Androgen Receptors with Elevated Potency for Antiandrogen-Resistant Receptor Mutants in Prostate Cancer: Tetra-Aryl-Substituted Cyclobutanes." June 2014. Link to Item
- Journal Articles
  - Tria, GS, Abrams, T, Baird, J, Burks, HE, Firestone, B, Gaither, LA, Hamann, LG, He, G, Kirby, CA, Kim, S, Lombardo, F, Macchi, KJ, McDonnell, DP, Mishina, Y, Norris, JD, Nunez, J, Springer, C, Sun, Y, Thomsen, NM, Wang, C, Wang, J, Yu, B, Tiong-Yip, C-L, and Peukert, S. "Discovery of LSZ102, a Potent, Orally Bioavailable Selective Estrogen Receptor Degrader (SERD) for the Treatment of Estrogen Receptor Positive Breast Cancer." Journal of medicinal chemistry (March 22, 2018). Full Text
  - McDonnell, DP, Norris, JD, and Chang, C-Y. "Neomorphic ERα Mutations Drive Progression in Breast Cancer and Present a Challenge for New Drug Discovery." Cancer Cell 33, no. 2 (February 2018): 153-155. Full Text Open Access Copy
  - Norris, JD, Ellison, SJ, Baker, JG, Stagg, DB, Wardell, SE, Park, S, Alley, HM, Baldi, RM, Yllanes, A, Andreano, KJ, Stice, JP, Lawrence, SA, Eisner, JR, Price, DK, Moore, WR, Figg, WD, and McDonnell, DP. "Androgen receptor antagonism drives cytochrome P450 17A1 inhibitor efficacy in prostate cancer." The Journal of Clinical Investigation 127, no. 6 (June 2017): 2326-2338. Full Text
  - Stice, JP, Wardell, SE, Norris, JD, Yllanes, AP, Alley, HM, Haney, VO, White, HS, Safi, R, Winter, PS, Cocce, KJ, Kishton, RJ, Lawrence, SA, Strum, JC, and McDonnell, DP. "CDK4/6 Therapeutic Intervention and Viable Alternative to Taxanes in CRPC." Molecular cancer research : MCR 15, no. 6 (June 2017): 660-669. Full Text
  - Burks, HE, Abrams, T, Kirby, CA, Baird, J, Fekete, A, Hamann, LG, Kim, S, Lombardo, F, Loo, A, Lubicka, D, Macchi, K, McDonnell, DP, Mishina, Y, Norris, JD, Nunez, J, Saran, C, Sun, Y, Thomsen, NM, Wang, C, Wang, J, and Peukert, S. "Discovery of an Acrylic Acid Based Tetrahydroisoquinoline as an Orally Bioavailable Selective Estrogen Receptor Degrader for ERα+ Breast Cancer." Journal of Medicinal Chemistry 60, no. 7 (April 2017): 2790-2818. Full Text
  - Christenson, JL, Butterfield, KT, Spoelstra, NS, Norris, JD, Josan, JS, Pollock, JA, McDonnell, DP, Katzenellenbogen, BS, Katzenellenbogen, JA, and Richer, JK. "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." Hormones & Cancer 8, no. 2 (April 2017): 69-77. Full Text
  - Pollock, JA, Wardell, SE, Parent, AA, Stagg, DB, Ellison, SJ, Alley, HM, Chao, CA, Lawrence, SA, Stice, JP, Spasojevic, I, Baker, JG, Kim, SH, McDonnell, DP, Katzenellenbogen, JA, and Norris, JD. "Inhibiting androgen receptor nuclear entry in castration-resistant prostate cancer." Nature Chemical Biology 12, no. 10 (October 2016): 795-801. Full Text
  - Wardell, SE, Ellis, MJ, Alley, HM, Eisele, K, VanArsdale, T, Dann, SG, Arndt, KT, Primeau, T, Griffin, E, Shao, J, Crowder, R, Lai, J-P, Norris, JD, McDonnell, DP, and Li, S. "Efficacy of SERD/SERM Hybrid-CDK4/6 Inhibitor Combinations in Models of Endocrine Therapy-Resistant Breast Cancer." Clinical Cancer Research : an Official Journal of the American Association for Cancer Research 21, no. 22 (November 2015): 5121-5130. Full Text
  - Gustafson, JL, Neklesa, TK, Cox, CS, Roth, AG, Buckley, DL, Tae, HS, Sundberg, TB, Stagg, DB, Hines, J, McDonnell, DP, Norris, JD, and Crews, CM. "Small-Molecule-Mediated Degradation of the Androgen Receptor through Hydrophobic Tagging." Angewandte Chemie (International Ed. in English) 54, no. 33 (August 2015): 9659-9662. Full Text
  - Gustafson, JL, Neklesa, TK, Cox, CS, Roth, AG, Buckley, DL, Tae, HS, Sundberg, TB, Stagg, DB, Hines, J, McDonnell, DP, Norris, JD, and Crews, CM. "Small-Molecule-Mediated Degradation of the Androgen Receptor through Hydrophobic Tagging." Angewandte Chemie International Edition 54, no. 33 (August 1, 2015): 9659-9662. Full Text
  - McDonnell, DP, Wardell, SE, and Norris, JD. "Oral Selective Estrogen Receptor Downregulators (SERDs), a Breakthrough Endocrine Therapy for Breast Cancer." Journal of Medicinal Chemistry 58, no. 12 (June 3, 2015): 4883-4887. Full Text
  - McDonnell, DP, Park, S, Goulet, MT, Jasper, J, Wardell, SE, Chang, C-Y, Norris, JD, Guyton, JR, and Nelson, ER. "Obesity, cholesterol metabolism, and breast cancer pathogenesis." Cancer Research 74, no. 18 (September 2014): 4976-4982. Full Text
  - Shatnawi, A, Norris, JD, Chaveroux, C, Jasper, JS, Sherk, AB, McDonnell, DP, and Giguère, V. "ELF3 is a repressor of androgen receptor action in prostate cancer cells." Oncogene 33, no. 7 (February 13, 2014): 862-871. Full Text
  - Shatnawi, A, Norris, JD, Chaveroux, C, Jasper, JS, Sherk, AB, McDonnell, DP, and Giguère, V. "ELF3 is a repressor of androgen receptor action in prostate cancer cells." Oncogene 33, no. 7 (February 2014): 862-871. Full Text
  - Teng, C, Goodwin, B, Shockley, K, Xia, M, Huang, R, Norris, J, Merrick, BA, Jetten, AM, Austin, CP, and Tice, RR. "Bisphenol A affects androgen receptor function via multiple mechanisms." Chemico Biological Interactions 203, no. 3 (May 2013): 556-564. Full Text
  - Norris, JD, Chang, C-Y, Wittmann, BM, Kunder, RS, Cui, H, Fan, D, Joseph, JD, and McDonnell, DP. "The homeodomain protein HOXB13 regulates the cellular response to androgens." Mol Cell 36, no. 3 (November 13, 2009): 405-416. Full Text Link to Item
  - Frigo, DE, Sherk, AB, Wittmann, BM, Norris, JD, Wang, Q, Joseph, JD, Toner, AP, Brown, M, and McDonnell, DP. "Induction of Kruppel-like factor 5 expression by androgens results in increased CXCR4-dependent migration of prostate cancer cells in vitro." Molecular Endocrinology (Baltimore, Md.) 23, no. 9 (September 2009): 1385-1396. Full Text
  - Joseph, JD, Wittmann, BM, Dwyer, MA, Cui, H, Dye, DA, McDonnell, DP, and Norris, JD. "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): 12178-12183. Full Text Link to Item
  - Norris, JD, Joseph, JD, Sherk, AB, Juzumiene, D, Turnbull, PS, Rafferty, SW, Cui, H, Anderson, E, Fan, D, Dye, DA, Deng, X, Kazmin, D, Chang, C-Y, Willson, TM, and McDonnell, DP. "Differential presentation of protein interaction surfaces on the androgen receptor defines the pharmacological actions of bound ligands." Chem Biol 16, no. 4 (April 24, 2009): 452-460. Full Text Link to Item
  - Sherk, AB, Frigo, DE, Schnackenberg, CG, Bray, JD, Laping, NJ, Trizna, W, Hammond, M, Patterson, JR, Thompson, SK, Kazmin, D, Norris, JD, and McDonnell, DP. "Development of a small-molecule serum- and glucocorticoid-regulated kinase-1 antagonist and its evaluation as a prostate cancer therapeutic." Cancer Research 68, no. 18 (September 2008): 7475-7483. Full Text
  - Kazmin, D, Prytkova, T, Cook, CE, Wolfinger, R, Chu, T-M, Beratan, D, Norris, JD, Chang, C-Y, and McDonnell, DP. "Linking ligand-induced alterations in androgen receptor structure to differential gene expression: a first step in the rational design of selective androgen receptor modulators." Molecular Endocrinology (Baltimore, Md.) 20, no. 6 (June 2006): 1201-1217. Full Text
  - Wu, Y-L, Yang, X, Ren, Z, McDonnell, DP, Norris, JD, Willson, TM, and Greene, GL. "Structural basis for an unexpected mode of SERM-mediated ER antagonism." Molecular Cell 18, no. 4 (May 2005): 413-424. Full Text
  - Juzumiene, D, Chang, C-Y, Fan, D, Hartney, T, Norris, JD, and McDonnell, DP. "Single-step purification of full-length human androgen receptor." Nucl Recept Signal 3 (2005): e001-. Full Text Link to Item
  - Chang, C-Y, Norris, JD, Jansen, M, Huang, H-J, and McDonnell, DP. "Application of random peptide phage display to the study of nuclear hormone receptors." Methods in Enzymology 364 (January 2003): 118-142. Full Text
  - Huang, H-J, Norris, JD, and McDonnell, DP. "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." Molecular Endocrinology (Baltimore, Md.) 16, no. 8 (August 2002): 1778-1792. Full Text
  - McDonnell, DP, Wijayaratne, A, Chang, C-Y, and Norris, JD. "Elucidation of the molecular mechanism of action of selective estrogen receptor modulators." Am J Cardiol 90, no. 1A (July 3, 2002): 35F-43F. (Review) Link to Item
  - McDonnell, DP, Wijayaratne, A, Chang, CY, and Norris, JD. "Elucidation of the molecular mechanism of action of selective estrogen receptor modulators." AMERICAN JOURNAL OF CARDIOLOGY 90, no. 1 (July 3, 2002): 35F-43F. Full Text Link to Item
  - McDonnell, DP, and Norris, JD. "Connections and regulation of the human estrogen receptor." Science (New York, N.Y.) 296, no. 5573 (May 2002): 1642-1644. (Review) Full Text
  - Norris, JD, Fan, D, Sherk, A, and McDonnell, DP. "A negative coregulator for the human ER." Molecular Endocrinology (Baltimore, Md.) 16, no. 3 (March 2002): 459-468. Full Text
  - McDonnell, DP, Connor, CE, Wijayaratne, A, Chang, C-Y, and Norris, JD. "Definition of the molecular and cellular mechanisms underlying the tissue-selective agonist/antagonist activities of selective estrogen receptor modulators." Recent Progress in Hormone Research 57 (January 2002): 295-316. (Review) Full Text
  - McDonnell, DP, Wijayaratne, A, Chang, C-Y, and Norris, JD. "Elucidation of the molecular mechanism of action of selective estrogen receptor modulators." American Journal of Cardiology 90, no. 1 SUPPL. 1 (2002): 35F-43F.
  - McDonnell, DP, Chang, CY, and Norris, JD. "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. Link to Item
  - McDonnell, DP, Connor, CE, Hall, J, Chang, CY, Jansen, MS, and Norris, JD. "The molecular pharmacology of estrogen receptor agonists, antagonists and SERMs." BONE 28, no. 5 (May 2001): S68-S68. Link to Item
  - Connor, CE, Norris, JD, Broadwater, G, Willson, TM, Gottardis, MM, Dewhirst, MW, and McDonnell, DP. "Circumventing tamoxifen resistance in breast cancers using antiestrogens that induce unique conformational changes in the estrogen receptor." Cancer Research 61, no. 7 (April 2001): 2917-2922.
  - Norris, JD, Chang, C, and McDonnell, DP. "Estrogen receptor-cofactor interactions as targets for novel drug discovery." Ernst Schering Res Found Workshop , no. 34 (2001): 181-201. (Review) Link to Item
  - McDonnell, DP, Chang, CY, and Norris, JD. "Development of peptide antagonists that target estrogen receptor-cofactor interactions." J Steroid Biochem Mol Biol 74, no. 5 (November 30, 2000): 327-335. (Review) Link to Item
  - Tcherepanova, I, Puigserver, P, Norris, JD, Spiegelman, BM, and McDonnell, DP. "Modulation of estrogen receptor-alpha transcriptional activity by the coactivator PGC-1." J Biol Chem 275, no. 21 (May 26, 2000): 16302-16308. Full Text Link to Item
  - Chang, CY, Norris, JD, Grøn, H, Paige, LA, Hamilton, PT, Kenan, DJ, Fowlkes, D, and McDonnell, DP. "Dissection of the LXXLL nuclear receptor-coactivator interaction motif using combinatorial peptide libraries: discovery of peptide antagonists of estrogen receptors alpha and beta." Molecular and Cellular Biology 19, no. 12 (December 1999): 8226-8239. Full Text
  - Wijayaratne, AL, Nagel, SC, Paige, LA, Christensen, DJ, Norris, JD, Fowlkes, DM, and McDonnell, DP. "Comparative Analyses of Mechanistic Differences Among Antiestrogens1." Endocrinology 140, no. 12 (December 1999): 5828-5840.
  - Wijayaratne, AL, Nagel, SC, Paige, LA, Christensen, DJ, Norris, JD, Fowlkes, DM, and McDonnell, DP. "Comparative analyses of mechanistic differences among antiestrogens." Endocrinology 140, no. 12 (December 1999): 5828-5840. Full Text
  - Norris, JD, Paige, LA, Christensen, DJ, Chang, CY, Huacani, MR, Fan, D, Hamilton, PT, Fowlkes, DM, and McDonnell, DP. "Peptide antagonists of the human estrogen receptor." Science (New York, N.Y.) 285, no. 5428 (July 1999): 744-746. Full Text
  - Paige, LA, Christensen, DJ, Grøn, H, Norris, JD, Gottlin, EB, Padilla, KM, Chang, CY, Ballas, LM, Hamilton, PT, McDonnell, DP, and Fowlkes, DM. "Estrogen receptor (ER) modulators each induce distinct conformational changes in ER alpha and ER beta." Proceedings of the National Academy of Sciences of the United States of America 96, no. 7 (March 1999): 3999-4004. Full Text
  - Norris, JD, Fan, D, Stallcup, MR, and McDonnell, DP. "Enhancement of estrogen receptor transcriptional activity by the coactivator GRIP-1 highlights the role of activation function 2 in determining estrogen receptor pharmacology." The Journal of Biological Chemistry 273, no. 12 (March 1998): 6679-6688. Full Text
  - Wagner, BL, Norris, JD, Knotts, TA, Weigel, NL, and McDonnell, DP. "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): 1369-1378. Link to Item
  - Ramamoorthy, K, Wang, F, Chen, I-C, Safe, S, Norris, JD, McDonnell, DP, Gaido, KW, Bocchinfuso, WP, Korach, KS, Ashby, J, Lefevre, PA, Odum, J, Harris, CA, Routledge, EJ, and Sumpter, JP. "Potency of combined estrogenic pesticides: Synergy between synthetic oestrogens?." Chemtracts 11, no. 4 (1998): 306-308.
  - Willson, TM, Norris, JD, Wagner, BL, Asplin, I, Baer, P, Brown, HR, Jones, SA, Henke, B, Sauls, H, Wolfe, S, Morris, DC, and McDonnell, DP. "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): 3901-3911. Full Text
  - Norris, JD, Fan, D, Kerner, SA, and McDonnell, DP. "Identification of a third autonomous activation domain within the human estrogen receptor." Molecular Endocrinology (Baltimore, Md.) 11, no. 6 (June 1997): 747-754. Full Text
  - Ramamoorthy, K, Wang, F, Chen, IC, Norris, JD, McDonnell, DP, Leonard, LS, Gaido, KW, Bocchinfuso, WP, Korach, KS, and Safe, S. "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): 1520-1527. Full Text
  - Ramamoorthy, K, Wang, F, Chen, IC, Safe, S, Norris, JD, McDonnell, DP, Gaido, KW, Bocchinfuso, WP, and Korach, KS. "Potency of combined estrogenic pesticides." Science 275, no. 5298 (January 17, 1997): 405-406. (Letter) Link to Item
  - Marks, JR, Huper, G, Vaughn, JP, Davis, PL, Norris, J, McDonnell, DP, Wiseman, RW, Futreal, PA, and Iglehart, JD. "BRCA1 expression is not directly responsive to estrogen." Oncogene 14, no. 1 (January 1997): 115-121. Full Text
  - McDonnell, DP, and Norris, JD. "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-S34. (Review) Link to Item
  - Norris, J, Fan, D, and McDonnell, DP. "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 (1997): 341--.
  - Fan, JD, Wagner, BL, and McDonnell, DP. "Identification of the sequences within the human complement 3 promoter required for estrogen responsiveness provides insight into the mechanism of tamoxifen mixed agonist activity." Molecular Endocrinology (Baltimore, Md.) 10, no. 12 (December 1996): 1605-1616. Full Text
  - Petranka, J, Zhao, J, Norris, J, Tweedy, NB, Ware, RE, Sims, PJ, and Rosse, WF. "Structure-function relationships of the complement regulatory protein, CD59." Blood Cells Mol Dis 22, no. 3 (1996): 281-296. Full Text Link to Item
  - Norris, J, Fan, D, Aleman, C, Marks, JR, Futreal, PA, Wiseman, RW, Iglehart, JD, Deininger, PL, and McDonnell, DP. "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): 22777-22782. Link to Item
  - Norris, J, Hall, S, Ware, RE, Kamitani, T, Chang, HM, Yeh, E, and Rosse, WF. "Glycosyl-phosphatidylinositol anchor synthesis in paroxysmal nocturnal hemoglobinuria: partial or complete defect in an early step." Blood 83, no. 3 (February 1994): 816-821.

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Education, Training, & Certifications

Duke Appointment History

Selected Grants

Selected Publications

Conference Papers

Journal Articles