Office: 548 Salk Hall
Paul Johnston is research Associate Professor in the department of Pharmaceutical Sciences, School of Pharmacy at the University of Pittsburgh. He obtained a B.Sc. with Honors (2.1) (1978) and a Ph.D. (1983) in Biochemistry, from the University of East Anglia in Norwich, England. Subsequent postdoctoral positions in the department of Pharmacology at the University of North Carolina, the Pathology department of Duke University, and at the Howard Hughes Institute of the University of Texas Southwestern have provided a diversity of experience in biochemistry, molecular biology, cell biology, immunology, protein purification and recombinant protein expression.
Dr Johnston has twenty four years of drug discovery experience in the Pharmaceutical, Biotechnology and academic sectors. In 1990 he joined American Cyanamid as a senior research Immunologist and project leader in drug discovery. Two years later he was recruited into the biotechnology sector by Embrex as a Group leader, and was later promoted to manager of discovery projects.
In 1997 he joined Sphinx Pharmaceuticals, which became Eli Lilly Research Triangle Park (Lilly-RTP), as a research scientist and was later promoted to research advisor. AT Lilly-RTP he directed an in vitro ADME/Tox hit characterization program and was an innovator of cell based approaches to lead generation and optimization, and pioneered the development and implementation of high content imaging technology to drug discovery. At Lilly, he led the development and implementation of 45 assays for high throughput screens and hit assessment campaigns that yielded hits for the lead generation efforts of 22 targets representing 4 therapeutic areas and diverse target classes; kinases, transporters, GPCR's, ion channels and multidrug resistance. To date these screens have produced 2 program sanctions, 6 leads, 1 ongoing hit-to-lead effort, and 3 ongoing hit assessment efforts.
He also directed the biology effort on three hit-to-lead optimization programs, and provided bioavailability information on hits and leads for 23 projects. In 2005, he joined the department of Pharmacology and Chemical Biology and the University of Pittsburgh Drug Discovery Institute to design and build a high throughput screening center where he has led twenty one screening campaigns, and reconfigured the NCI 60 cell line assays for cancer drug combination screening. In 2011, Dr. Johnston joined the Department of Pharmaceutical Sciences in the School of Pharmacy to establish chemical biology laboratories and continued his research in HTS/HCS assay development and implementation, and established collaborations throughout the scientific community.
1. Johnston, P.A. and A. Coddington (1982). Multiple Drug Resistance in the Fission Yeast Schizosaccharomyces pombe: Evidence for the Existence of Pleiotropic Mutations Affecting Energy Dependent Transport systems. Mol. Gen. Genet. 185: 311-314.
2. Johnston, P.A. and A. Coddington (1983). Multiple Drug Resistance in the Fission Yeast Schizosaccharomyces pombe: Correlation between Drug and Amino Acid Uptake and Membrane ATPase Activities. Current Genetics 7: 299-307.
3. Johnston, P.A. and A. Coddington (1984). Drug Resistance in the Fission Yeast Schizosaccharomyces pombe: Pleiotropic Mutations Affecting the Oleic Acid and Sterol Composition of Cell Membranes. Current Genetics 8: 37-43.
4. Johnston, P.A., D.O. Adams, and T.A. Hamilton (1984). Fc-receptor-Mediated Protein Phosphorylation in Murine Peritoneal Macrophages. Biochem. Biophys. Res. Commun. 124: 197-202.
5. Johnston, P.A., D.O. Adams, and T.A. Hamilton (1985). Regulation of the Fc-receptor-mediated Respiratory Burst: Treatment of Primed Murine Peritoneal macrophages with Lipopolysaccharide Selectively Inhibits H202 Secretion Stimulated by Immune Complexes. J. Immunol.135: 513-518.
6. Johnston, P.A., D.O. Adams and T.A. Hamilton (1986). Regulation of Respiratory Burst in Murine Peritoneal macrophages: Differential Sensitivity to Phorbol Diesters by Macrophages in Different Stages of Functional Activation. Cell. Immunol. 100: 400-410.
7. Johnston, P.A., M.M Jansen, S.D. Somers, D.O. Adams and T.A. Hamilton (1987). Ligands for the Scavenger Receptor on Murine Peritoneal Macrophages Induce Expression of a Set of Early Proteins. J. Immunol. 138: 1551-1558.
8. Johnston, P.A. S.D. Somers and T.A. Hamilton (1987). Expression of a 120 Kilodalton Protein During Tumoricidal Activation in Murine Peritoneal Macrophages. J. Immunol. 138: 2739-2744.
9. Introna, M., R.C. Bast, Jr., P.A. Johnston, D.O. Adams and T.A. Hamilton (1987). Homologous and Heterologous Desensitization of Proto-Oncogene cFos Expression in Murine Peritoneal Macrophages. J. Cell. Physiol. 131: 36-42.
10. Johnston, P.A., T.J. Koerner, M.M. Jansen and T.A. Hamilton (1989). Expression of Macrophage p120 Depends upon Early Protein Synthesis. J. Immunol. 142: 2728-2735.
11. Johnston, P.A., G.A. Reynolds, S. Wasserman and T.C. Sudhof (1990). Two Novel Annexins from Drosophila Melanogaster. Cloning, Characterization and Differential Expression in Development. J. Biol. Chem 265: 11382-11388.
12. Johnston, P.A., F. Yu, G.A. Reynolds, H.L. Yin, C.R. Moomaw, C.A. Slaughter C.A. and T.A. Sudhof (1990). Purification and Expression of gCap39. An Intracellular and Secreted Ca2+-Dependent Actin-Binding Protein Enriched in Mononuclear Phagocytes. J. Biol. Chem. 265: 17946-17952.
13. Yu, Fu-Xin, P.A. Johnston, T.C. Sudhof and H.L. Yin (1990). gCap39, a Calcium Ion and Polyphosphoinositide-Regulated Actin Capping Protein. Science 250: 1413-1415.
14. Johnston, P.A. and T.C. Sudhof (1990). Evolutionary Conservation and Structure-Function Relationships in the Calelectrins (Annnexins). Biochem. Soc. Trans. 18: 1097-1098.
15. Perrin, M., P.A. Johnston, T. Ozcelik, R. Jahn, U. Franke and T.C. Sudhof (1991). Structural and Functional Conservation of Synaptotagnin p65) in Drosophila and Humans. J. Biol. Chem. 266: 615-622.
16. Mignery, G.A., P.A. Johnston and T.C. Sudhof (1992). Mechanism of Ca2+ Inhibition of Inositol 1,4,5-Trisphosphate (InsP3) Binding to the Cerebellar InsP3 Receptor. J. Biol. Chem. 267: 7450-7455.
17. Daley, M.J., G. Furda, R. Dougherty, P.A. Coyle, T.J. Williams and P.A. Johnston (1992). Potentiation of Antibiotic Therapy for Bovine Mastitis by Recombinant Bovine Interleukin-2. J. Dairy Science 75: 3330-3338.
18. Tao, W.T., R. Dougherty, P.A. Johnston and W. Pickett (1993). Recombinant Bovine GM-CSF Primes Platlet Activating Factor, rHuIL-8 but not rBoIL-1 Induced Bovine Neutrophil Degranulation. J. Leukocyte Biology 53: 679-684.
19. Bolnet, C., P.A. Johnston, A. Kemper, C. Ricks, & J. Petite (1995). Influence of Avian Con A Induced Splenocyte Conditioned Media on Cells of the Hematopoietic Lineage. J. Poultry Sci. 74: 1102-1116.
20. Johnston, P. A. and P. A. Johnston (2002). Cellular Platforms for HTS: three case studies. Drug Discovery Today 7: 353-363.
21. Pratt S, Shepard RL, Kandasamy RA, Johnston PA, Perry W 3rd, and Dantzig AH. (2005). The multidrug resistance protein 5 (ABCC5) confers resistance to 5-fluorouracil and transports its monophosphorylated metabolites. Mol. Cancer Ther. 4:855-63.
22. Razonable RR, Henault M, Lee LN, Laethem C, Johnston PA, Watson HL, Paya CV. (2005) Secretion of proinflammatory cytokines and chemokines during amphotericin B exposure is mediated by coactivation of toll-like receptors 1 and 2 Antimicrob Agents Chemother. 49(4):1617-21.
23. Arnold DM, Foster C, Huryn DM, Lazo JS, Johnston PA, Wipf P. (2007) Synthesis and Biological Activity of a Focused Library of Mitogen-activated Protein Kinase Phosphatase Inhibitors. Chem. Biol. Drug Des. 69:23-30.
24. Brisson-Tierno M*, Johnston PA*, Foster C, Skoko JJ, Shun TY, Lazo JS. (2007) Development and Optimization of high-throughput in vitro protein phosphatase screening assays for drug discovery. * Authors contributed equally to this work. Nature Protocols. 2:1134-44.
25. Johnston PA. An interview with Paul A. Johnston, Ph.D., by Vicki Glaser. (2007) Assay and Drug Development Technologies. 5: 289-97.
26. Johnston PA, Foster CA, Shun TY, Skoko JJ, Shinde S, Wipf P, and Lazo JS. (2007) Development and Implementation of a 384-well Homogeneous Fluorescence Intensity HTS Assay to Identify Mitogen-Activated Protein Kinase Phosphatase-1 Dual Specificity Protein Phosphatase Inhibitors. Assays and Drug. Discovery Technologies. 5: 319-332.
27. Johnston PA, Phillips J, Shun TY, Shinde SN, Lazo JS, Huryn DM, Myers MC, Ratnikov BI, Smith JW, Su Y, Dahl R, Cosford NDP, Shiryaev SA, and Strongin AY. (2007) HTS Identifies Novel and Specific Uncompetitive Inhibitors of the Two-Component NS2B-NS3 Proteinase of West Nile Virus. Assay and Drug Development Technologies. Assays and Drug. Discovery Technologies. 5: 737-750.
28. Keinan S, Paquette WD, Skoko JJ, Beratan DN, Yang W, Shinde S, Johnston PA, Lazo JS, and Wipf P. (2008) Computational design, synthesis and biological evaluation of para-quinone-based inhibitors for redox regulation of the dual-specificity phosphatase Cdc25B. Org. Biomol. Chem. 6: 3256-3263.
29. Johnston PA, Soares KM, Shinde SN, Foster CA, Shun TY, Takyi HK, Wipf P, and Lazo JS. (2008) Development of a 384-well Colorimetric Assay to Quantify Hydrogen Peroxide Generated by the Redox Cycling of Compounds in the Presence of Reducing Agents. Assay and Drug Development Technologies. 6: 505-518.
30. Johnston PA, Foster CA, Tierno MB, Shun TY, Shinde SN, Paquette WD, Brummond KM, Wipf P, and Lazo JS. (2009). Cdc25B Dual Specificity Phosphatase Inhibitors Identified in a High Throughput Screen of the NIH Compound Library. Assay and Drug Development Technologies. 7: 250-265.
31. Kay M. Brummond, Shuli Mao, Sunita N. Shinde, Paul A. Johnston, and Billy W. Day. (2009). Design and Synthesis of a Library of Tetracyclic Hydroazulenoisoindoles. J. Comb. Chem., 11: 486-494.
32. Wipf P, Arnold D, Carter K, Dong S, Johnston PA, Sharlow E, Lazo JS, Huryn D. (2009). A case study from the chemistry core of the Pittsburgh Molecular Library Screening Center: the Polo-like kinase polo-box domain (Plk1-PBD). Curr Top Med Chem., 9:1194-205.
33. Soares KM, Blackmon N, Shun TY, Shinde SN, Takyi HK, Wipf P, Lazo JS, Johnston PA. (2010). Profiling the NIH Small Molecule Repository for Compounds That Generate H(2)O(2) by Redox Cycling in Reducing Environments. Assay Drug Dev Technol. 8: 152-171.
34. Dudgeon D, Shinde, SN, Shun, TY, Lazo, JS, Strock, CJ, Giuliano, KA, Taylor, DL, Johnston, PA, and Johnston, PA. (2010). Characterization and Optimization of a Novel Protein-Protein Interaction Biosensor HCS Assay to Identify Disruptors of the Interactions between p53 and hDM2. Assay Drug Dev Technol. 8: 437-58.
35. Dudgeon D, Shinde, SN, Hua, Y, Shun, TY, Lazo, JS, Strock, CJ, Giuliano, KA, Taylor, DL, Johnston, PA, and Johnston, PA. (2010). Implementation of a 220,000 Compound HCS Campaign to Identify Disruptors of the Interaction between p53 and hDM2, and Characterization of the Confirmed Hits. J Biomol Screen. 15: 766-782.
36. Gosai SJ, Kwak JH, Luke CJ, Long OS, King DE, Kovatch KJ, Johnston PA, Shun TY, Lazo JS, Perlmutter DH, Silverman GA and Pak SC. (2010) Automated high –content live animal drug screening using C. elegans expressing the aggregation prone serpin α1-antitrypsin Z. PLoS One. 2010 Nov 12;5(11):e15460.
37. Shun TY, Lazo JS, Sharlow ER, Johnston PA. (2011) Identifying Actives from HTS Data Sets, Practical Approaches for the Selection of an Appropriate HTS Data Processing Method and Quality Control Review. J Biomol Screen. 16: 1-14.
38. Daghestani HN, Zhu G, Johnston PA, Shinde SN, Brodsky JL, Vallee RB, and Day BW. (2011) "Characterization of Inhibitors of Glucocorticoid Receptor Nuclear Translocation: A Model of Cytoplasmic Dynein-Mediated Cargo Transport" Assay Drug Dev Technol. Sep 15. [Epub ahead of print]
REVIEWS, PROCEEDINGS OF CONFERENCE & SYMPOSIA, & BOOK CHAPTERS:
1. P. A. Johnston, H. Liu, T. O'Connell, P. Phelps, M. Bland, J. Tyczkowski, A. Kemper, T. Harding, A. Avakian, E. Haddad, C. Whitfill, R. Gildersleeve, and C. Ricks (1995). Proceedings of the Symposium - Current Advances in Avian Embryology and Incubation, Session V: Interventions in Embryo Development. Applications of In ovo Technology". J. Poultry Sci. 76: (1) 165-178.
2. Carpenter, J; C. Laethem, F. R. Hubbard, T. K. Eckols, M. Baez, D. McClure, D. L. G. Nelson, and P. A. Johnston. (2002). Configuring Radioligand receptor Binding Assays for HTS using Scintillation Proximity Assay Technology. High Throughput Screening: Methods and Protocols, in Methods in Molecular Biology, 190: 31-49. The Humana Press, Inc. Edited by W. P. Janzen.
3. A. H. Gough and P. A. Johnston. (2006) Requirements, Features and Performance of High Content Screening Platforms, in High Content Screening: A Powerful Approach to Systems Cell Biology and Drug Discovery. Methods in Molecular Biology 356: 41-61. Humana Press, Totowa, NJ. Editors: D. L. Taylor, J. R. Haskins and K.A. Giuliano
4. R.G.Williams, R.Kandasamy, D.Nickischer, O.J. Trask, C.Laethem, P.A Johnston, and P.A. Johnston. (2006). “Generation and Characterization of a Stable MK2-EGFP Cell Line and Subsequent Development of a High Content Imaging Assay on the Cellomics ArrayScan® Platform to Screen for p38 MAPK Inhibitors” in Methods in Enzymology 414: 364-89. “Automated Microscopy Screening” Elsevier/Academic Press Edited by Jim Inglese.
5. O.J. Trask, A.Baker, R.G.Williams, D.Nickischer, R. Kandasamy, C. Laethem, P. A. Johnston, and P. A. Johnston. (2006). “Assay Development and Case History of a 32K Biased Library High Content MK2-EGFP Translocation Screen to Identify p38 MAPK Inhibitors on the ArrayScan® 3.1 Imaging Platform” in Methods in Enzymology 414: 419-39. “Automated Microscopy Screening” Elsevier/Academic Press Edited by Jim Inglese.
6. D. Nickischer, C. L. Laethem, O. J. Trask, Jr., R. G. Williams, R. Kandasamy, P. A. Johnston, and P. A. Johnston. (2006). “Development and implementation of three MAPK signaling pathway imaging assays to provide MAPK module selectivity profiling for kinase inhibitors; MK2-EGFP translocation, c-Jun & ERK activation” in Methods in Enzymology 414: 389-418. “Automated Microscopy Screening” Elsevier/Academic Press Edited by Jim Inglese.
7. P. A. Johnston. (2007) “Automated High Content Screening Microscopy” Chapter 2, p25-42, in High Content Screening: Science, Technology and Applications. John Wiley & Sons, Inc; Edited by: Stephen A. Haney.
8. Trask OJ, Nickischer D, Burton A, Williams RG, Kandasamy RA, Johnston PA, Johnston PA. (2009). High-throughput automated confocal microscopy imaging screen of a kinase-focused library to identify p38 mitogen-activated protein kinase inhibitors using the GE InCell 3000 analyzer. Methods Mol Biol. 565:159-186.
9. P. A. Johnston. (2011). Redox cycling compounds generate H(2)O(2) in HTS buffers containing strong reducing reagents - real hits or promiscuous artifacts? Curr Opin Chem Biol. 15(1):174-82.
10. P. A. Johnston and J. R. Grandis. (2011). STAT3 signaling: anticancer strategies and challenges. Mol Interv. 2011 Feb;11(1):18-26.
11. P. A. Johnston. (2012) High content analysis and screening: basics, instrumentation and applications. Chemical Genomics. Cambridge University Press, Edited by: Haian Fu.