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McDonald, Patricia
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McDonald, Patricia

Faculty Member
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Positions

  • 2017 - 2018 Associate Professor, Molecular Medicine , Scripps Research
  • 2010 - 2018 Faculty Member, Skaggs Graduate School of Chemical and Biological Sciences , Scripps Research
  • 2005 - 2018 Associate Scientific Director I, Translational Research Institute , Scripps Research
  • 2010 - 2017 Assistant Professor of Molecular Therapeutics (Joint Appointment), Molecular Therapeutics , Scripps Research
  • 2002 - 2005 Research Scientist, Eli Lilly & Company
  • 2000 - 2002 Senior Scientist, DuPont Pharmaceuticals
  • 1995 - 2000 Senior Postdoctoral Fellow, School of Medicine, Duke University
  • 1993 - 1994 Postdoctoral Fellow, University of Glasgow
Dr. Patricia McDonald focuses on the development of biochemical and cell-based functional assays to identify and develop small molecule modulators of GPCRs for the treatment of metabolic and CNS disorders.

Research Areas research areas

  • Drug Discovery (UMLS)

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  • Laboratory Website
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Publications

recent publications

  • academic article

    • Levine, P. M., Balana, A. T., Sturchler, E., Koole, C., Noda, H., Zarzycka, B., Daley, E. J., Truong, T. T., Katritch, V., Gardella, T. J., Wootten, D., Sexton, P. M., et al. O-GlcNAc engineering of GPCR peptide-agonists improves their stability and in vivo activity Journal of the American Chemical Society  2019 141:14210-14219  DOI:10.1021/jacs.9b05365  PMID:31418572
    • Bailey, T. L., Nieto, A., McDonald, P. H. A Nonradioactive High-Throughput Screening-Compatible Cell-Based Assay to Identify Inhibitors of the Monocarboxylate Transporter Protein 1 Assay and Drug Development Technologies  2019 17:275-284  DOI:10.1089/adt.2019.936  PMID:31532712
    • Zuo, H., Glaaser, I., Zhao, Y. L., Kurinov, I., Mosyak, L., Wang, H. N., Liu, J., Park, J., Frangaj, A., Sturchler, E., Zhou, M., McDonald, P., et al. Structural basis for auxiliary subunit KCTD16 regulation of the GABA(B) receptor Proceedings of the National Academy of Sciences of the United States of America  2019 116:8370-8379  DOI:10.1073/pnas.1903024116  PMID:30971491  PMCID:PMC6486783
    • Nieto, A., Fernandez-Vega, V., Spicer, T. P., Sturchler, E., Adhikari, P., Kennedy, N., Mandat, S., Chase, P., Scampavia, L., Bannister, T., Hodder, P., McDonald, P. H. Identification of Novel, Structurally Diverse, Small Molecule Modulators of GPR119 Assay and Drug Development Technologies  2018 16:278-288  DOI:10.1089/adt.2018.849  PMID:30019946  PMCID:PMC6065524
    • Gutierrez, A. N., McDonald, P. H. GPCRs: Emerging anti-cancer drug targets Cellular Signalling  2017 41:65-74  DOI:10.1016/j.cellsig.2017.09.005  PMID:28931490
    • Li, X., Sturchler, E., Kaczanowska, K., Cameron, M., Finn, M. G., Griffin, P., McDonald, P., Markou, A. KK-92A, a novel GABAB receptor positive allosteric modulator, attenuates nicotine self-administration and cue-induced nicotine seeking in rats. Psychopharmacology  2017 234:1633-1644  DOI:10.1007/s00213-017-4594-9  PMID:28382542
    • Geng, Y., Mosyak, L., Kurinov, I., Zuo, H., Sturchler, E., Cheng, T. C., Subramanyam, P., Brown, A. P., Brennan, S. C., Mun, H. C., Bush, M., Chen, Y., et al. Structural mechanism of ligand activation in human calcium-sensing receptor Elife  2016 5  DOI:10.7554/eLife.13662  PMID:27434672  PMCID:PMC4977154
    • Zhang, H., Sturchler, E., Zhu, J., Nieto, A., Cistrone, P. A., Xie, J., He, L., Yea, K., Jones, T., Turn, R., Di Stefano, P. S., Griffin, P. R., et al. Autocrine selection of a GLP-1R G-protein biased agonist with potent antidiabetic effects Nature Communications  2015 6:8918  DOI:10.1038/ncomms9918  PMID:26621478  PMCID:PMC4686834
    • Robinson, J. D., McDonald, P. H. The orexin 1 receptor modulates kappa opioid receptor function via a JNK-dependent mechanism Cellular Signalling  2015 27:1449-1456  DOI:10.1016/j.cellsig.2015.03.026  PMID:25857454
    • Dabul, S., Bathgate-Siryk, A., Valero, T. R., Jafferjee, M., Sturchler, E., McDonald, P., Koch, W. J., Lymperopoulos, A. Suppression of adrenal beta arrestin1-dependent aldosterone production by ARBs: head-to-head comparison Scientific Reports  2015 5:8116  DOI:10.1038/srep08116  PMID:25631300  PMCID:PMC4309955
    • Di Fruscia, P., He, Y., Koenig, M., Tabrizifard, S., Nieto, A., McDonald, P. H., Kamenecka, T. M. The discovery of indole full agonists of the neurotensin receptor 1 (NTSR1) Bioorganic & Medicinal Chemistry Letters  2014 24:3974-3978  DOI:10.1016/j.bmcl.2014.06.033  PMID:24997685  PMCID:PMC4130903
    • Sturchler, E., Chen, W., Spicer, T., Hodder, P., McDonald, P., Duckett, D. Development of an HTS-compatible assay for the discovery of ASK1 signalosome inhibitors using alphascreen technology Assay and Drug Development Technologies  2014 12:229-237  DOI:10.1089/adt.2013.558  PMID:24831789  PMCID:PMC4025566
    • Robinson, J., Smith, A., Sturchler, E., Tabrizifard, S., Kamenecka, T., McDonald, P. Development of a high-throughput screening-compatible cell-based functional assay to identify small molecule probes of the galanin 3 receptor (GalR3) Assay and Drug Development Technologies  2013 11:468-477  DOI:10.1089/adt.2013.526  PMID:24116939  PMCID:PMC3804082
    • Sturchler, E., Feurstein, D., Chen, W. M., McDonald, P., Duckett, D. Stress-induced nuclear import of apoptosis signal-regulating kinase 1 is mediated by karyopherin alpha 2/beta 1 heterodimer Biochimica et Biophysica Acta-Molecular Cell Research  2013 1833:583-592  DOI:10.1016/j.bbamcr.2012.10.023  PMID:23123190
    • Begriche, K., Girardet, C., McDonald, P., Butler, A. A. Melanocortin-3 receptors and metabolic homeostasis Progress In Molecular Biology and Translational Science  2013 114:109-146  DOI:10.1016/b978-0-12-386933-3.00004-2  PMID:23317784
    • Jiang, R., Song, X. Y., Bali, P., Smith, A., Bayona, C. R., Lin, L., Cameron, M. D., McDonald, P. H., Kenny, P. J., Kamenecka, T. M. Disubstituted piperidines as potent orexin (hypocretin) receptor antagonists Bioorganic & Medicinal Chemistry Letters  2012 22:3890-3894  DOI:10.1016/j.bmcl.2012.04.122  PMID:22617492  PMCID:PMC3383661
    • Begriche, K., Marston, O. J., Rossi, J., Burke, L. K., McDonald, P., Heisler, L. K., Butler, A. A. Melanocortin-3 receptors are involved in adaptation to restricted feeding Genes Brain and Behavior  2012 11:291-302  DOI:10.1111/j.1601-183X.2012.00766.x  PMID:22353545  PMCID:PMC3319531
    • McDonald, P., Sturchler, E. GPCRs: new opportunities and challenges for drug discovery European Pharmaceutical Review  2012 17
    • Bohn, L. M., McDonald, P. H. Detecting the role of arrestins in G protein-coupled receptor regulation Neuromethods  2011 60:347-358  DOI:10.1007/978-1-61779-179-6_17
    • Sturchler, E., Feurstein, D., McDonald, P., Duckett, D. Mechanism of oxidative stress-induced ASK1-catalyzed MKK6 phosphorylation Biochemistry  2010 49:4094-4102  DOI:10.1021/bi100010j  PMID:20364819
    • McDonald, P., Sturchler, E. Exploring GPCR desensitization using label-free technology: implications in early drug discovery International Drug Discovery  2010 6:48-54
    • Bohn, L. M., McDonald, P. H. Seeking ligand bias: assessing GPCR coupling to beta-arrestins for drug discovery Drug Discovery Today. Technologies  2010 7:e37-e42  DOI:10.1016/j.ddtec.2010.06.005  PMID:21218149  PMCID:PMC3014586
    • Brothers, S. P., Saldanha, S. A., Spicer, T. P., Cameron, M., Mercer, B. A., Chase, P., McDonald, P., Wahlestedt, C., Hodder, P. S. Selective and brain penetrant neuropeptide y y2 receptor antagonists discovered by whole-cell high-throughput screening Molecular Pharmacology  2010 77:46-57  DOI:10.1124/mol.109.058677  PMID:19837904  PMCID:PMC2802430
    • Pachori, A. S., Smith, A., McDonald, P., Zhang, L., Dzau, V. J., Melo, L. G. Heme-oxygenase-1-induced protection against hypoxia/reoxygenation is dependent on biliverdin reductase and its interaction with PI3K/Akt pathway Journal of Molecular and Cellular Cardiology  2007 43:580-592  DOI:10.1016/j.yjmcc.2007.08.003  PMID:17920074  PMCID:PMC2699998
    • Berglund, M. M., Schober, D. A., Statnick, M. A., McDonald, P. H., Gehlert, D. R. The use of bioluminescence resonance energy transfer 2 to study neuropeptide Y receptor agonist-induced beta-arrestin 2 interaction Journal of Pharmacology and Experimental Therapeutics  2003 306:147-156  DOI:10.1124/jpet.103.051227  PMID:12665544
    • Kohout, T. A., Takaoka, H., McDonald, P. H., Perry, S. J., Mao, L., Lefkowitz, R. J., Rockman, H. A. Augmentation of cardiac contractility mediated by the human beta(3)-adrenergic receptor overexpressed in the hearts of transgenic mice Circulation  2001 104:2485-2491  DOI:10.1161/hc4501.098933  PMID:11705829
    • Shenoy, S. K., McDonald, P. H., Kohout, T. A., Lefkowitz, R. J. Regulation of receptor fate by ubiquitination of activated beta(2)-adrenergic receptor and beta-arrestin Science  2001 294:1307-1313  DOI:10.1126/science.1063866  PMID:11588219
    • McDonald, P. H., Lefkowitz, R. J. Beta arrestins: New roles in regulating heptahelical receptors' functions Cellular Signalling  2001 13:683-689  DOI:10.1016/s0898-6568(01)00203-0  PMID:11602178
    • Miller, W. E., McDonald, P. H., Cai, S. F., Field, M. E., Davis, R. J., Lefkowitz, R. J. Identification of a motif in the carboxyl terminus of β-arrestin2 responsible for activation of JNK3 Journal of Biological Chemistry  2001 276:27770-27777  DOI:10.1074/jbc.M102264200  PMID:11356842
    • McDonald, P. H., Chow, C. W., Miller, W. E., Laporte, S. A., Field, M. E., Lin, F. T., Davis, R. J., Lefkowitz, R. J. Beta-arrestin 2: a receptor-regulated MAPK scaffold for the activation of JNK3 Science  2000 290:1574-1577  DOI:10.1126/science.290.5496.1574  PMID:11090355
    • Alexander, M. Y., Webster, K. A., McDonald, P. H., Prentice, H. M. Gene transfer and models of gene therapy for the myocardium Clinical and Experimental Pharmacology and Physiology  1999 26:661-668  DOI:10.1046/j.1440-1681.1999.03117.x  PMID:10499153
    • Kypson, A. P., Hendrickson, S. C., Akhter, S. A., Wilson, K., McDonald, P. H., Lilly, R. E., Dolber, P. C., Glower, D. D., Lefkowitz, R. J., Koch, W. J. Adenovirus-mediated gene transfer of the beta(2)-adrenergic receptor to donor hearts enhances cardiac function Gene Therapy  1999 6:1298-1304  DOI:10.1038/sj.gt.3300940  PMID:10455439
    • Maurice, J. P., Hata, J. A., Shah, A. S., White, D. C., McDonald, P. H., Dolber, P. C., Wilson, K. H., Lefkowitz, R. J., Glower, D. D., Koch, W. J. Enhancement of cardiac function after adenoviral-mediated in vivo intracoronary beta(2)-adrenergic receptor gene delivery Journal of Clinical Investigation  1999 104:21-29  DOI:10.1172/jci6026  PMID:10393695
    • McDonald, P. H., Cote, N. L., Lin, F. T., Premont, R. T., Pitcher, J. A., Lefkowitz, R. J. Identification of NSF as a beta-arrestin1-binding protein - implications for beta(2)-adrenergic receptor regulation Journal of Biological Chemistry  1999 274:10677-10680  DOI:10.1074/jbc.274.16.10677  PMID:10196135
    • Akhter, S. A., Skaer, C. A., Kypson, A. P., McDonald, P. H., Peppel, K. C., Glower, D. D., Lefkowitz, R. J., Koch, W. J. Restoration of beta-adrenergic signaling in failing cardiac ventricular myocytes via adenoviral-mediated gene transfer Proceedings of the National Academy of Sciences of the United States of America  1997 94:12100-12105  DOI:10.1073/pnas.94.22.12100  PMID:9342369  PMCID:PMC23716
    • Peppel, K., Boekhoff, I., McDonald, P., Breer, H., Caron, M. G., Lefkowitz, R. J. G protein-coupled receptor kinase 3 (GRK3) gene disruption leads to loss of odorant receptor desensitization Journal of Biological Chemistry  1997 272:25425-25428  DOI:10.1074/jbc.272.41.25425  PMID:9325250
    • McDonald, P., Hicks, M. N., Cobbe, S. M., Prentice, H. Gene transfer in models of myocardial ischemia Annals of the New York Academy of Sciences  1995 752:455-459  DOI:10.1111/j.1749-6632.1995.tb17455.x  PMID:7755291
    • Da Cruz e Silva, E. F., Hughes, V., McDonald, P., Stark, M. J. R., Cohen, P. T. W. Protein phosphatase 2Bw and protein phosphatase Z are Saccharomyces cerevisiae enzymes Biochimica et Biophysica Acta  1991 1089:269-272  DOI:10.1016/0167-4781(91)90023-F  PMID:1647215
  • report

    • Saldanha, S. A., Brothers, S. P., Spicer, T., Cameron, M., Mercer, B. A., Chase, P., McDonald, P., Wahlestedt, C., Hodder, P. S. Probe report for NPY-Y2 receptor antagonists Probe Reports from the NIH Molecular Libraries Program. 2010  PMID:21433370

featured in

  • Scripps Research Institute Scientists in Florida Awarded $2.3 Million NIH Grant to Develop New Treatments for Drug Addiction  News Release
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Research

research overview

  • G-protein-coupled receptors (GPCRs) represent the largest and most versatile family of cell surface receptors. The ubiquitous cell surface distribution and involvement of these proteins in virtually all biological processes accounts for the fact that the largest percentage of currently marketed therapeutic drugs target GPCRs. Work in our laboratory is focused on the development of biochemical and cell-based functional assays to monitor GPCR activity using both high throughput and high content technologies. In collaboration with other disciplines such as chemistry, DMPK and in vivo pharmacology we aim to identify and develop small molecule modulators of GPCRs for the therapeutic treatment of metabolic and CNS disorders.
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Teaching

advisees

  • graduate advising relationship

    • Bailey, Tracey Elizabeth, Ph.D.  candidate, 2017 -
    • Adhikari, Pramisha, Ph.D.  candidate, 2014 - 2018
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Background

education and training

  • Ph.D. in Molecular Genetics, The University of Dundee 1993
  • Diploma in Pharmaceutical Studies, University of North London , with Distinction 1989
  • B.S. in Biology and Chemistry, University of North London , with Honors 1989
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Contact

full name

  • Patricia McDonald

geographic location

  • Scripps Florida 

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