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 G - Education (NCI)
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Shafik, Hasnaa
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Sloan-Kettering Institute for Cancer Research
New York
United States
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Orlow, I; Satagopan, J M; Berwick, M et al. (2015) Genetic factors associated with naevus count and dermoscopic patterns: preliminary results from the Study of Nevi in Children (SONIC). Br J Dermatol 172:1081-9
Carey, Bryce W; Finley, Lydia W S; Cross, Justin R et al. (2015) Intracellular ?-ketoglutarate maintains the pluripotency of embryonic stem cells. Nature 518:413-6
Mosher, C E; Given, B A; Ostroff, J S (2015) Barriers to mental health service use among distressed family caregivers of lung cancer patients. Eur J Cancer Care (Engl) 24:50-9
Navi, Babak B; Reiner, Anne S; Kamel, Hooman et al. (2015) Association between incident cancer and subsequent stroke. Ann Neurol 77:291-300
Xu, Zhe; Wu, Chaochao; Xie, Fang et al. (2015) Comprehensive quantitative analysis of ovarian and breast cancer tumor peptidomes. J Proteome Res 14:422-33
Xu, Hong; Cheng, Ming; Guo, Hongfen et al. (2015) Retargeting T cells to GD2 pentasaccharide on human tumors using Bispecific humanized antibody. Cancer Immunol Res 3:266-77
Gondo, Tatsuo; Poon, Bing Ying; Matsumoto, Kazuhiro et al. (2015) Clinical role of pathological downgrading after radical prostatectomy in patients with biopsy confirmed Gleason score 3 + 4 prostate cancer. BJU Int 115:81-6
Das, Sudeep; Thorek, Daniel L J; Grimm, Jan (2014) Cerenkov imaging. Adv Cancer Res 124:213-34
Fay, Allison; Glickman, Michael S (2014) An essential nonredundant role for mycobacterial DnaK in native protein folding. PLoS Genet 10:e1004516
Ripley, R Taylor; McMillan, Robert R; Sima, Camelia S et al. (2014) Second primary lung cancers: smokers versus nonsmokers after resection of stage I lung adenocarcinoma. Ann Thorac Surg 98:968-74

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