Directory Profile

Paul A. Johnston, PhD
Professor, Pharmaceutical Sciences

BIOGRAPHY:

Paul Johnston is 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-nine 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. Dr. Johnston teaches biochemistry and drug discovery courses to students in the Pharm.D. and Ph.D. programs of the School of Pharmacy, and he is a member of the Biochemical Pharmacology and Medicinal Chemistry tracks of the graduate program.

Research Interest

RESEARCH INTERESTS:

Throughout his career Dr. Johnston has been 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. A founding member of the Society for Biomolecular Imaging and Informatics (SBI2) in 2012, he is a past president of the society. In 2011, Dr. Johnston joined the Department of Pharmaceutical Sciences in the School of Pharmacy where he established his own chemical biology laboratories and his research has focused on the application of novel drug discovery strategies to identify new and effective drugs or drug combinations for prostate cancer, melanoma, head and neck cancer, and hepatocellular carcinoma. He also provides expertise in HTS/HCS assay development and implementation for drug discovery collaborations in other therapeutic areas. Dr. Johnston teaches biochemistry and drug discovery courses to students in the Pharm.D. and Ph.D. programs of the School of Pharmacy. Hi is a member of the Biochemical Pharmacology and Medicinal Chemistry tracks of the graduate program.

Publications

PUBLICATIONS (81 Total) https://www.ncbi.nlm.nih.gov/myncbi/1zC76Lsfbmv5v/bibliography/public/

REFEREED ARTICLES (2014-2019):

1. Johnston, PA, Sen, M, Hua, Y, Camarco, D, Shun, TY, Lazo, JS, and Grandis JR. (2014) High Content pSTAT3/1 Imaging Assays to Screen for Selective Inhibitors of STAT3 Pathway Activation in Head and Neck Cancer Cell Lines. Assay Drug Dev Technol. 2014 Jan-Feb;12 (1):55-79. doi: 10.1089/adt.2013.524. Epub 2013 Oct 15.
2. Yun Hua, Tong Ying Shun, Christopher J. Strock, and Paul A. Johnston, (2014) High Content Biosensor Assay to Identify Compounds that Prevent or Disrupt Androgen Receptor and Transcription Intermediary Factor 2 Co-activator Protein-Protein Interactions. Assay Drug Dev Technol. Sep;12(7):395-418. doi: 10.1089/adt.2014.594.
3. LaPorte MG, da Paz Lima DJ, Zhang F, Sen M, Grandis JR, Camarco D, Hua Y, Johnston PA, Lazo JS, Resnick LO, Wipf P, Huryn DM. (2014) "2-Guanidinoquinazolines as new inhibitors of the STAT3 pathway." Bioorg Med Chem Lett. 2014 Nov 1;24(21):5081-5. doi: 10.1016/j.bmcl.2014.09.001. Epub 2014 Sep 15.
4. George Rosenker KM, Paquette WD, Johnston PA, Sharlow ER, Vogt A, Bakan A, Lazo JS, Wipf P. (2015) “Synthesis and biological evaluation of 3-aminoisoquinolin-1(2H)-one based inhibitors of the dual-specificity phosphatase Cdc25B.” Bioorg Med Chem. 2015 Jan 31. pii: S0968-0896(15)00067-X. doi: 10.1016/j.bmc.2015.01.043.
5. Zhiwei Feng, Stanton Kochanek, David Close, LiRong Wang, Ajay Srinivasan, Abdulrahman A. Almehizia, Prema Iyer, Xiang-Qun Xie, Paul A. Johnston, and Barry Gold. (2015). “Design and activity of AP endonuclease-1 inhibitors”. J. Chemical Biology, 2015 8(3):79-93.
6. Van Allen EM, Lui VW, Egloff AM, Goetz EM, Li H, Johnson JT, Duvvuri U, Bauman JE, Stransky N, Zeng Y, Gilbert BR, Pendleton KP, Wang L, Chiosea S, Sougnez C, Wagle N, Zhang F, Du Y, Close D, Johnston PA, McKenna A, Carter SL, Golub TR, Getz G, Mills GB, Garraway LA, Grandis JR. (2015) “Genomic Correlate of Exceptional Erlotinib Response in Head and Neck Squamous Cell Carcinoma.” JAMA Oncol. 2015, 1(2):238-44
7. Singh M, Close DA, Mukundan S, Johnston PA, Sant S. (2015) “Production of Uniform 3D Microtumors in Hydrogel Microwell Arrays for Measurement of Viability, Morphology, and Signaling Pathway Activation. Assay Drug Dev Technol. 2015. 13(9):570-83. doi: 10.1089/adt.2015.662. Epub 2015 Aug 14. PMID: 26274587
8. Johnston PA, Sen M, Hua Y, Camarco DP, Shun TY, Lazo JS, Wilson GM, Resnick LO, LaPorte MG, Wipf P, Huryn DM, Grandis JR. (2015) “HCS Campaign to Identify Selective Inhibitors of IL-6-Induced STAT3 Pathway Activation in Head and Neck Cancer Cell Lines.” Assay Drug Dev Technol. 2015 Sep;13(7):356-76. doi: 10.1089/adt.2015.663.
9. Johnston PA, Nguyen MM, Dar JA, Ai J, Wang Y, Masoodi KZ, Shun T, Shinde S, Camarco DP, Hua Y, Huryn DM, Wilson GM, Lazo JS, Nelson JB, Wipf P, Wang Z. (2016) Development and Implementation of a High-Throughput High-Content Screening Assay to Identify Inhibitors of Androgen Receptor Nuclear Localization in Castration-Resistant Prostate Cancer Cells. Assay Drug Dev Technol. 2016 May;14(4):226-39. doi: 10.1089/adt.2016.716. PMID: 27187604
10. Johnson JK, Skoda EM, Zhou J, Parrinello E, Wang D, O'Malley K, Eyer BR, Kazancioglu M, Eisermann K, Johnston PA, Nelson JB, Wang Z, Wipf P. Small Molecule Antagonists of the Nuclear Androgen Receptor for the Treatment of Castration-Resistant Prostate Cancer. ACS Med Chem Lett. 2016 May 27;7(8):785-90. doi: 10.1021/acsmedchemlett.6b00186. PMID: 27563404; PMCID: PMC4983742.
11. LaPorte MG, Wang Z, Colombo R, Garzan A, Peshkov VA, Liang M, Johnston PA, Schurdak ME, Sen M, Camarco DP, Hua Y, Pollock NI, Lazo JS, Grandis JR, Wipf P, Huryn DM. (2016) Optimization of pyrazole-containing 1,2,4-triazolo-[3,4-b]thiadiazines, a new class of STAT3 pathway inhibitors. Bioorg Med Chem Lett. 2016 Jun 9. pii: S0960-894X(16)30628-X. doi: 10.1016/j.bmcl.2016.06.017. PMID: 27381083
12. Fancher AT, Hua Y, Camarco DP, Close DA, Strock CJ, Johnston PA. Reconfiguring the AR-TIF2 Protein-Protein Interaction HCS Assay in Prostate Cancer Cells and Characterizing the Hits from a LOPAC Screen. Assay Drug Dev Technol. 2016 Oct;14(8):453-477. PubMed PMID: 27606620.
13. Kiesel BF, Parise RA, Guo J, Huryn DM, Johnston PA, Colombo R, Sen M, Grandis JR, Beumer JH, Eiseman JL. Toxicity, pharmacokinetics and metabolism of a novel inhibitor of IL-6-induced STAT3 activation. Cancer Chemother Pharmacol. 2016, Dec;78(6):1225-1235. PMID: 27778071
14. Sen, M, Johnston PA, Pollock NI, DeGrave K, Joyce SC, Freilino ML, Hua Y, Camarco DP, Close DA, Huryn DM, Wipf P, & Grandis JR. Mechanism of action of selective inhibitors of IL-6 induced Stat3 pathway in head and neck cancer cell lines. J Chem Biol. 2017 May 11;10(3):129-141. doi: 10.1007/s12154-017-0169-9. eCollection 2017 Jul. PMID: 28684999
15. Masoodi KZ, Xu Y, Dar JA, Eisermann K, Pascal LE, Parrinello E, Ai J, Johnston PA, Nelson JB, Wipf P, Wang Z. Inhibition of Androgen Receptor Nuclear Localization and Castration Resistant Prostate Tumor Growth by Pyrroloimidazole-Based Small Molecules. Mol Cancer Ther. 2017 Jun 27. pii: molcanther.0176.2017. doi: 10.1158/1535-7163.MCT-17-0176. [Epub ahead of print] PMID: 28655783
16. Masoodi KZ, Eisermann K, Yang Z, Dar JA, Pascal LE, Nguyen M, O'Malley K, Parrinello E, Feturi FG, Kenefake AN, Nelson JB, Johnston PA, Wipf P, Wang Z. Inhibition of Androgen Receptor Function and Level in Castration-Resistant Prostate Cancer Cells by 2-[(isoxazol-4-ylmethyl)thio]-1-(4-phenylpiperazin-1-yl)ethanone. Endocrinology. 2017 Oct 1;158(10):3152-3161. doi: 10.1210/en.2017-00408. PMID: 28977599
17. Shan F, Close DA, Camarco DP, Johnston PA. High-Content Screening Comparison of Cancer Drug Accumulation and Distribution in Two-Dimensional and Three-Dimensional Culture Models of Head and Neck Cancer. Assay Drug Dev Technol. 2018 Jan;16(1):27-50. doi: 10.1089/adt.2017.812. Epub 2017 Dec 7. PMID: 29215913
18. Fancher AT, Hua Y, Camarco DP, Close DA, Strock CJ, Johnston PA. High-Content Screening Campaign to Identify Compounds That Inhibit or Disrupt Androgen Receptor-Transcriptional Intermediary Factor 2 Protein-Protein Interactions for the Treatment of Prostate Cancer. Assay Drug Dev Technol. 2018 Aug/Sep;16(6):297-319. doi: 10.1089/adt.2018.858. Epub 2018 Aug 15. PMID: 30109944
19. Close DA, Wang AX, Kochanek SJ, Shun T, Eiseman JL, Johnston PA. Implementation of the NCI-60 Human Tumor Cell Line Panel to Screen 2260 Cancer Drug Combinations to Generate >3 Million Data Points Used to Populate a Large Matrix of Anti-Neoplastic Agent Combinations (ALMANAC) Database. SLAS Discov. 2019 Mar;24(3):242-263. doi: 10.1177/2472555218812429. Epub 2018 Nov 30. PMID: 30500310
20. Kochanek SJ, Close DA, Johnston PA. High Content Screening Characterization of Head and Neck Squamous Cell Carcinoma Multicellular Tumor Spheroid Cultures Generated in 384-Well Ultra-Low Attachment Plates to Screen for Better Cancer Drug Leads. Assay Drug Dev Technol. 2019 Jan;17(1):17-36. doi: 10.1089/adt.2018.896. Epub 2018 Dec 28. PMID: 30592624
21. Kochanek SJ, Close DA, Wang AX, Shun T, Empey PE, Eiseman JL, Johnston PA. Confirmation of Selected Synergistic Cancer Drug Combinations Identified in an HTS Campaign and Exploration of Drug Efflux Transporter Contributions to the Mode of Synergy. SLAS Discov. 2019 Apr 30:2472555219844566. doi: 10.1177/2472555219844566.PMID: 31039321

REVIEWS, PROCEEDINGS OF CONFERENCE & SYMPOSIA, & BOOK CHAPTERS:

1. Trask OJ, and Johnston PA. (2014). Introduction and welcome to the Society of Biomolecular Imaging and Informatics (SBI²). Assay Drug Dev Technol. 2014 Sep;12(7):369-74. doi: 10.1089/adt.2014.1506. PMID:25181409.
2. Yun Hua, Christopher J. Strock and Paul A. Johnston, “High Content Screening Biosensor Assay to Identify Disruptors of p53-hDM2 Protein-Protein Interactions.” Methods Mol Biol. 2015; 1278:555-65. doi: 10.1007/978-1-4939-2425-7_37. 2nd edition of “Protein-Protein Interactions: Methods and Applications” edited by Haian Fu and Cheryl Meyerkord, published by Humana Press, part of Springer Science and Business Media.
3. Trask OJ Jr, and Johnston PA. (2015). “Standardization of High Content Imaging and Informatics.” Assay Drug Dev Technol. 2015 Sep;13(7):341-6. doi: 10.1089/adt.2015.29022.ojt
4. Sant, S & Johnston PA. 2017 “The Production of 3D Tumor Spheroids for Cancer Drug Discovery”. Drug Discov Today Technol. 2017 Mar; 23:27-36. doi: 10.1016/j.ddtec.2017.03.002. Epub 2017 Apr 14. Review. PMID: 28647083.
5. Johnston P.A., Trask O.J. (Editors) (2018) High Content Screening. Methods in Molecular Biology, Vol 1683. Humana Press, New York, NY
6. Hua Y., Camarco D.P., Strock C.J., Johnston P.A. (2018) High Content Positional Biosensor Assay to Screen for Compounds that Prevent or Disrupt Androgen Receptor and Transcription Intermediary Factor 2 Protein-Protein Interactions. In: Johnston P., Trask O. (Eds) High Content Screening. Methods in Molecular Biology, Vol 1683: pp 211-227. Humana Press, New York, NY DOI https://doi.org/10.1007/978-1-4939-7357-6_13
7. Johnston P.A., Sen M, Hua Y, Camarco DP, Shun TY, Lazo JS, Grandis JR. (2018) High Content Imaging Assays for IL-6-Induced STAT3 Pathway Activation in Head and Neck Cancer Cell Lines. In: Johnston P., Trask O. (Mds) High Content Screening. Methods in Molecular Biology, Vol 1683. pp 239- 244. Humana Press, New York, NY DOI https://doi.org/10.1007/978-1-4939-7357-6_14
8. Close D.A., Camarco D.P., Shan F., Kochanek S.J., Johnston P.A. (2018) The Generation of Three-Dimensional Head and Neck Cancer Models for Drug Discovery in 384-Well Ultra-Low Attachment Microplates. In: Johnston P., Trask O. (Eds) High Content Screening. Methods in Molecular Biology, Vol 1683: pp 355-369. Humana Press, New York, NY DOI https://doi.org/10.1007/978-1-4939-7357-6_20

Presentations

INVITED PRESENTATIONS (2014-2019):

1. Paul A. Johnston, Dan Camarco & Nancy C. Reich. “Prosecution of a STAT3 Nuclear Localization HCS Campaign Utilizing the Dotmatics Solutions”. Dotmatics East Coast User Group Meeting. (5-JUNE-2014). Museum of Science, Boston, USA
2. Paul A. Johnston. “High Throughput Screening to Identify Synergistic Cancer Drug Combinations?” (30-MAR-2015) Invited speaker for the Interdisciplinary Toxicology Graduate Program and Departmental Seminar Series at Texas A & M University, College Station, TX.
3. Paul A. Johnston. “Targeting AR-TIF2 Coactivator Interactions in Castration Resistant Prostate Cancer.” (23-APR-2015) Society of Biomolecular Imaging and Informatics (SBI2) East Coast Regional Meeting at the North Carolina Biotechnology Center, Research Triangle Park, NC.
4. Paul A. Johnston. “Strategies to Identify Synergistic Cancer Drug Combinations using High Throughput Screening?” (11-JUNE-2015) Gulf Coast Consortium (GCC) Drug Discovery Conference entitled “Recent Advances in the Development of Combinatorial Therapies for Cancer” in the Biosciences Research Collaborative (BRC) building, Rice University, Houston, TX.
5. Paul A. Johnston. Altered Cancer Drug Responses in 2D and 3D Cell Culture Models of Head and Neck Cancer. (17-SEPT-2015) Society of Biomolecular Imaging and Informatics (SBI2) 2nd Annual Conference at Joseph B. Martin Conference Center, Harvard Medical School, Boston, MA. Session III: Phenotypic Drug Discovery.
6. Paul A. Johnston. Finding Effective Drug Combinations for Melanoma. (December-11-2015). University of Pittsburgh Cancer Institute, Melanoma & Skin Cancer SPORE Research Progress Update.
7. Paul A. Johnston. “Targeting STAT3 pathway activation in Head and Neck Cancer.” (13-JUNE-2016) Gulf Coast Consortium (GCC) Drug Discovery Conference entitled “Application of Automated Microscopy and Image Informatics to Cancer Research” in the Biosciences Research Collaborative (BRC) building, Rice University, Houston, TX.
8. Paul A. Johnston. Comparing Cancer Drug Penetration in 2D and 3D Cell Culture Models of Head and Neck Cancer. (14-SEPT-2016) Society of Biomolecular Imaging and Informatics (SBI2) 3rd Annual Conference at Joseph B. Martin Conference Center, Harvard Medical School, Boston, MA. Session IV: Innovations in High Content Biology: 3D, Co-cultures and Stem Cell Systems, Poster Number: IV-1.
9. Paul A. Johnston. Unbiased high throughput drug combination screening identifies synergistic drug combinations effective in patient derived melanoma cell lines. (8-FEB-2017) 6th annual conference of the Society for Laboratory Automation and Screening (SLAS 2017) in Washington, DC. Track Name: Automation and High-Throughput Technologies, Session Title: Automating Novel Analytical Tools for PKA, Drug-Drug Combination and Synergy Assays, Drug Repurposing.
10. Paul A. Johnston. “Implementing 3D tumor models: a strategy to improve cancer drug development success rates?” (22-JUNE-2017) Keynote presentation at the 13th Asia Pacific Multidisciplinary Meeting for Cancer Research “Cancer 2017” Prince of Wales Hospital in Hong Kong.
11. Paul A. Johnston. “Development and Characterization of Patient Derived 3D Hepatocellular Carcinoma Organoid Models using HCS Methods and their Application to Precision Medicine and Drug Discovery.” Society of Biomolecular Imaging and Informatics (SBI2) 5th Annual Conference at Joseph B. Martin Conference Center, Harvard Medical School, Boston, MA. Presentation Date: September 20th, 2018, Session III. “Advancing and Expanding 3D and 4D Imaging Modes.”
12. Paul A. Johnston. “Development and Characterization of Patient Derived 3D Hepatocellular Carcinoma Organoid Models using HCS Methods and their Application to Precision Medicine and Drug Discovery.” Presented at the 6th annual conference of the Society for Laboratory Automation and Screening (SLAS) in Washington D.C., February 2019. Presentation Date: February 4th, 2019. Track name: Automation and High Throughput Technologies. Session title: Advancing imaging technologies to bridge the gap between high content and high throughput.
13. Paul A. Johnston. “Targeting Androgen Receptor Interactions with Transcription Intermediary Factor 2 to find Castration Resistant Prostate Cancer Drug Leads.” Molecular Biophysics/Structural Biology Departmental Seminar, February 21st, 2019, 6014 Biomedical Science Tower 3, University of Pittsburgh.

Grants

GRANTS (2014-2019)

ACTIVE:

NIH NCI R01 CA233622-01A1 (Hinck & Johnston Co-PIs) 07/01/2019- 06/30/2023
HTS for TGF‐β receptor assembly inhibitors with anti-tumor & anti-fibrosis activities

NIH NCI R01 CA229836-01A1 (Johnston PI) 04/01/2019- 03/31/2023
qHTS of Patient Derived HCC Models to Identify Novel Probes/Therapeutic Agents

COMPLETED:

Chinese University of Hong Kong Collaborative Research Agreement I # 0044080 (Wong PI) 12/01/2014 – 11/30/2018.
High throughput screening for Inhibitors of Liver Cancer Growth

NIH 1R01GM111086-01A1 (Smithgall PI) 12/01/2014 – 11/30/2018
High-throughput Discovery of Chemical Probes for HIV-1 Nef Function

NIH NCI 1R01CA183882-01A1 (Johnston PI) 05/01/2015- 04/30/2018
HCS to Identify Inhibitors and Disruptors of AR-TIF2 Interactions

Doris Duke Charitable Foundation (Burns PI) 7/1/15 -6/30/18
Targeting the TWIST1-E2A pathway in oncogene driven lung cancer

Head and Neck Cancer SPORE Development Research Project (Johnston PI)
University of Pittsburgh 2016-2017
Develop and implement 3D head and neck cancer spheroid cell culture models to screen for effective HNC drugs and drug combinations.

NIH 1R01DE023685-01A1 (Grandis PI) 05/01/2014 – 04/30/2019
PI3K Pathway Mutations in Head and Neck Cancer

NIH 2R01CA077308-16A1 (Grandis PI) 08/01/2014 – 05/31/2019
STAT Mediated TGF-A/EGFR Signaling in Squamous Cell Carcinomas of Head & Neck

University of Pittsburgh Melanoma & Skin Cancer SPORE Development Research Project (Johnston PI) 07/01/2014-06/30/2015
Identifying Synergy between APE1 DNA Repair Inhibitors and Approved Melanoma Cancer Drugs

NIH/NCI 1R01CA160423-01A1 Johnston (PI) 2012-2015
Development of a Novel HCS Assay to Screen for Disruptors of AR-TIF2 Interactions

Trainees

CV