The High-throughput Screening Core Facility (HTSCF) was established in 2003 to support the Institution's growth in chemical biology and functional genomics. The HTSCF's ongoing mission continues to support such efforts. Bioactive compounds are used as chemical tools to probe biological processes. The identification of novel molecules requires a broad range of tools including robust assays, large collections of chemicals, HTS technologies, and knowledge in hit validation and characterization steps. The HTSCF has modern robotics, custom built screening data management databases, chemical screening libraries, RNAi screening libraries, assay development and industrialization expertise, screening data analysis and management. The Core is equipped with two custom-built linear track robotic platforms harboring several dispensers, microtiter plate readers, automated microscopes among other instrumentation enabling both invitro target based and cell based assays to be routinely performed. Screening data acquisition and management is handled through a suite of custom built software. The compound library has grown to 400K chemicals; and contains a wide variety of natural products. The RNAi libraries have also grown to include both siRNA and shRNA capabilities covering 22K genes. Glycerol stocks of individual shRNA hairpins are provided as a service. One example of important work facilitated by this work was a screen against mutant EGFR in human lung cancer cell lines by the Varmus lab. The screening efforts led to the identification and characterization of four classes of small molecules overcoming the mutations. The broad range of services and collaborative work provided by the (HTSCF) has supported the research of 48 investigators in the past year. During the past grant period the work of the Core has contributed to 27 publications of researchers from 8 research programs.

Public Health Relevance

The HTS Core facility provides investigators with access to two established chemical biology and functional genomic platforms; where discovered chemical molecules are used as probes to study biological processes, and Identified active gene(s) are further studied in the context of target validation for therapeutic intervention.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Center Core Grants (P30)
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Subcommittee I - Transistion to Independence (NCI)
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Sloan-Kettering Institute for Cancer Research
New York
United States
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Basaraba, Cale N; Westhoff, Carolyn L; Pike, Malcolm C et al. (2017) Estimating systemic exposure to levonorgestrel from an oral contraceptive. Contraception 95:398-404
Hernandez, Jonathan M; Beylergil, Volkan; Goldman, Debra A et al. (2017) Post-Treatment/Pre-operative PET Response Is Not an Independent Predictor of Outcomes for Patients With Gastric and GEJ Adenocarcinoma. Ann Surg :
Argani, Pedram; Kao, Yu-Chien; Zhang, Lei et al. (2017) Primary Renal Sarcomas With BCOR-CCNB3 Gene Fusion: A Report of 2 Cases Showing Histologic Overlap With Clear Cell Sarcoma of Kidney, Suggesting Further Link Between BCOR-related Sarcomas of the Kidney and Soft Tissues. Am J Surg Pathol 41:1702-1712
Moore, Kathleen N; Martin, Lainie P; O'Malley, David M et al. (2017) Safety and Activity of Mirvetuximab Soravtansine (IMGN853), a Folate Receptor Alpha-Targeting Antibody-Drug Conjugate, in Platinum-Resistant Ovarian, Fallopian Tube, or Primary Peritoneal Cancer: A Phase I Expansion Study. J Clin Oncol 35:1112-1118
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Hyman, David M; Taylor, Barry S; Baselga, José (2017) Implementing Genome-Driven Oncology. Cell 168:584-599
Li, Gang G; Somwar, Romel; Joseph, James et al. (2017) Antitumor Activity of RXDX-105 in Multiple Cancer Types with RET Rearrangements or Mutations. Clin Cancer Res 23:2981-2990
Bhagat, Tushar D; Zou, Yiyu; Huang, Shizheng et al. (2017) Notch Pathway Is Activated via Genetic and Epigenetic Alterations and Is a Therapeutic Target in Clear Cell Renal Cancer. J Biol Chem 292:837-846
Prieto-Granada, Carlos N; Zhang, Lei; Antonescu, Cristina R et al. (2017) Primary cutaneous adenoid cystic carcinoma with MYB aberrations: report of three cases and comprehensive review of the literature. J Cutan Pathol 44:201-209
He, Mu; Agbu, Stephanie; Anderson, Kathryn V (2017) Microtubule Motors Drive Hedgehog Signaling in Primary Cilia. Trends Cell Biol 27:110-125

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