High-Throughput Screening

SARS-CoV-2 Pseudovirus

Neutralization Assay
Assay available in our High-Throughput Screening Lab
Test your COVID-19 therapeutic strategy against the SARS-CoV-2
Host cells with abundant ACE2 surface receptor

Mission

Our mission is to facilitate research conducted by OSU scientists and external clients in the areas of high-throughput and high-content screening of chemical libraries, assay development and optimization, bioactivity characterization, and automation services.

Services

• Screening Assay Development
• Primary and Secondary Compound Library Screening using in-house (300K small molecule and 10K natural product libraries) or client-provided library resources
• Custom plate generation (targeted compound sets, specific titration series)
• Automated workflow development
• High Content Screening using Thermo Cell Insight Platform
• Combinatorial Compound Library Screening
• Drug Synergy Testing
• Cytotoxicity Profiling & MIC Determinations
• Screening documentation and analysis using the Dotmatics Software Suite

Highlights

• Thousands of reagent plates were generated for Dr. Brian Druker’s laboratory in the OHSU Knight Cancer Institute resulting in a high-profile publication (Nature, 2018) 1
• Completed multiple bioactivity screens of up to 50,000 small molecules from in-house or compound libraries provided by outside investigators. 2-8
• Adopted a chloramphenicol acetyl transferase (CAT) assay for high-throughput screening. 9
• Developed and deployed a high-throughput toxicity assay for combinatorial cryoprotectant screening. 10
• Enabled the optimization and ongoing utilization of a functional bioluminescence-based assay essential to a new R01 grant from the NIH awarded in 2018 to Drs. Jane Ishmael (Pharmacology) and Kerry McPhail (Natural Products Chemistry) of the College of Pharmacy to pursue natural products drug discovery research.
• 170,000 compounds screened by Neuralexo, Inc. with 5 structures discovered for lead development.
• 280,000 compounds screened with an assay from Vaccine and Gene Therapy Institute at OHSU
• Collaboration between OSU researcher and Harvard’s ICCB-Longwood Screening Facility for RNAi screening via High-Content Imaging.
• Collaboration between OHSU researcher and Medicines for Malaria Ventures to screen proprietary library of 75,000 compounds against T. gondii.

^References

1. ^{Tyner JW, Tognon CE, Bottomly D, Wilmot B, Kurtz SE, Savage SL, Long N, Schultz AR, Traer E, Abel M, Agarwal A, Blucher A, Borate U, Bryant J, Burke R, Carlos A, Carpenter R, Carroll J, Chang BH, Coblentz C, d'Almeida A, Cook R, Danilov A, Dao KT, Degnin M, Devine D, Dibb J, Edwards DK 5th, Eide CA, English I, Glover J, Henson R, Ho H, Jemal A, Johnson K, Johnson R, Junio B, Kaempf A, Leonard J, Lin C, Liu SQ, Lo P, Loriaux MM, Luty S, Macey T, MacManiman J, Martinez J, Mori M, Nelson D, Nichols C, Peters J, Ramsdill J, Rofelty A, Schuff R, Searles R, Segerdell E, Smith RL, Spurgeon SE, Sweeney T, Thapa A, Visser C, Wagner J, Watanabe-Smith K, Werth K, Wolf J, White L, Yates A, Zhang H, Cogle CR, Collins RH, Connolly DC, Deininger MW, Drusbosky L, Hourigan CS, Jordan CT, Kropf P, Lin TL, Martinez ME, Medeiros BC, Pallapati RR, Pollyea DA, Swords RT, Watts JM, Weir SJ, Wiest DL, Winters RM, McWeeney SK, Druker BJ . Functional Genomic Landscape of Acute Myeloid Leukemia. Nature. 2018 Oct;562(7728):526-531. doi: 10.1038/s41586-018-0623-z}
2. ^{Carpenter EL, Chagani S, Nelson D, Cassidy PB, Laws M, Ganguli-Indra G, Indra AK. Mitochondrial complex I inhibitor deguelin induces metabolic reprogramming and sensitizes vemurafenib-resistant BRAFV600E mutation bearing metastatic melanoma cells. Mol Carcinog. 2019 Jun 18;. doi: 10.1002/mc.23068.}
3. ^{Billard B, Chang CN, Singh AJ, Gross MK, Allen R, Kioussi C. Phenotypic Screening of Drug Library in Actively Differentiating Mouse Embryonic Stem Cells. J Biomol Screen. 2016;21(4):399-407. doi:10.1177/1087057115624093.}
4. ^{Brown A, Patel S, Ward C, Lorenz A, Ortiz M, DuRoss A, Wieghardt F, Esch A, Otten EG, Heiser LM, Korolchuk VI, Sun C, Sarkar S, Sahay G. PEG-lipid micelles enable cholesterol efflux in Niemann-Pick Type C1 disease-based lysosomal storage disorder. Sci Rep. 2016;6:31750. doi:10.1038/srep31750.}
5. ^{Bonventre JA, Zielke RA, Korotkov KV, Sikora AE. Targeting an Essential GTPase Obg for the Development of Broad-Spectrum Antibiotics. Wieden H-J, ed. PLoS ONE. 2016;11(2):e0148222. doi:10.1371/journal.pone.0148222.}
6. ^{Alfadhli A, Mack A, Harper L, Berk S, Ritchie C, Barklis E. Analysis of Quinolinequinone Reactivity, Cytotoxicity, and Anti-HIV-1 Properties. Bioorg Med Chem. 2016;24(21):5618-5625. doi:10.1016/j.bmc.2016.09.028.}
7. ^{Donley N, Jaruga P, Coskun E, Dizdaroglu M, McCullough AK, Lloyd RS. Small Molecule Inhibitors of 8-Oxoguanine DNA Glycosylase-1 (OGG1). ACS Chem Bio. 2015;10(10):2334-2343. doi:10.1021/acschembio.5b00452.}
8. ^{Lue HW, Cole B, Rao SA, Podolak J, Van Gaest A, King C, Eide CA, Wilmot B, Xue C, Spellman PT, Heiser LM, Tyner JW, Thomas GV. Src and STAT3 inhibitors synergize to promote tumor inhibition in renal cell carcinoma. Oncotarget. 2015;6(42):44675-44687.}
9. ^{Wells K, Videau P, Nelson D, Eiting J, Philmus B. The role of sigma factors in recognition of cyanobacterial promoters: Towards Escherichia coli as a general heterologous expression host for cyanobacterial natural products. FEMS Microbol Lett. 2018 Aug 1;365(15). doi: 10.1093/femsle/fny164.}
10. ^{Warner R, Ampo E, Nelson D, Benson J, Eroglu A, Higgins AZ. High Throughput Screening for Development of Cyroprotectant Toxicity Cost Functions. Poster presented at: 56th Annual Meeting of the Society for Cyrobiology; 2019 July 22-25. San Diego, CA.}