Literature DB >> 24661215

Chemical & RNAi screening at MSKCC: a collaborative platform to discover & repurpose drugs to fight disease.

Bhavneet Bhinder, Christophe Antczak, David Shum, Constantin Radu, Jeni P Mahida, Nancy Liu-Sullivan, Glorymar Ibanez, Balajee Somalinga Raja, Paul A Calder, Hakim Djaballah1.   

Abstract

Memorial Sloan Kettering Cancer Center (MSKCC) has implemented the creation of a full service state-of-the-art High-throughput Screening Core Facility (HTSCF) equipped with modern robotics and custom-built screening data management resources to rapidly store and query chemical and RNAi screening data outputs. The mission of the facility is to provide oncology clinicians and researchers alike with access to cost-effective HTS solutions for both chemical and RNAi screening, with an ultimate goal of novel target identification and drug discovery. HTSCF was established in 2003 to support the institution's commitment to growth in molecular pharmacology and in the realm of therapeutic agents to fight chronic diseases such as cancer. This endeavor required broad range of expertise in technology development to establish robust and innovative assays, large collections of diverse chemical and RNAi duplexes to probe specific cellular events, sophisticated compound and data handling capabilities, and a profound knowledge in assay development, hit validation, and characterization. Our goal has been to strive for constant innovation, and we strongly believe in shifting the paradigm from traditional drug discovery towards translational research now, making allowance for unmet clinical needs in patients. Our efforts towards repurposing FDA-approved drugs fructified when digoxin, identified through primary HTS, was administered in the clinic for treatment of stage Vb retinoblastoma. In summary, the overall aim of our facility is to identify novel chemical probes, to study cellular processes relevant to investigator's research interest in chemical biology and functional genomics, and to be instrumental in accelerating the process of drug discovery in academia.

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Year:  2014        PMID: 24661215      PMCID: PMC4050342          DOI: 10.2174/1386207317666140323132222

Source DB:  PubMed          Journal:  Comb Chem High Throughput Screen        ISSN: 1386-2073            Impact factor:   1.339


  15 in total

1.  Superoxide dismutase 1 (SOD1) is a target for a small molecule identified in a screen for inhibitors of the growth of lung adenocarcinoma cell lines.

Authors:  Romel Somwar; Hediye Erdjument-Bromage; Erik Larsson; David Shum; William W Lockwood; Guangli Yang; Chris Sander; Ouathek Ouerfelli; Paul J Tempst; Hakim Djaballah; Harold E Varmus
Journal:  Proc Natl Acad Sci U S A       Date:  2011-09-19       Impact factor: 11.205

2.  Domain-based biosensor assay to screen for epidermal growth factor receptor modulators in live cells.

Authors:  Christophe Antczak; Alun Bermingham; Paul Calder; Dmitry Malkov; Keming Song; John Fetter; Hakim Djaballah
Journal:  Assay Drug Dev Technol       Date:  2012-01-26       Impact factor: 1.738

3.  Validation of a high-content screening assay using whole-well imaging of transformed phenotypes.

Authors:  Christina N Ramirez; Tatsuya Ozawa; Toshimitsu Takagi; Christophe Antczak; David Shum; Robert Graves; Eric C Holland; Hakim Djaballah
Journal:  Assay Drug Dev Technol       Date:  2010-12-23       Impact factor: 1.738

4.  High-throughput screening assay for the identification of compounds regulating self-renewal and differentiation in human embryonic stem cells.

Authors:  Sabrina C Desbordes; Dimitris G Placantonakis; Anthony Ciro; Nicholas D Socci; Gabsang Lee; Hakim Djaballah; Lorenz Studer
Journal:  Cell Stem Cell       Date:  2008-06-05       Impact factor: 24.633

5.  Identification and preliminary characterization of novel small molecules that inhibit growth of human lung adenocarcinoma cells.

Authors:  Romel Somwar; David Shum; Hakim Djaballah; Harold Varmus
Journal:  J Biomol Screen       Date:  2009-12

6.  Intra-arterial and oral digoxin therapy for retinoblastoma.

Authors:  Mrinali Patel; Yannis M Paulus; Y Pierre Gobin; Hakim Djaballah; Brian Marr; Ira J Dunkel; Scott Brodie; Christophe Antczak; Robert Folberg; David H Abramson
Journal:  Ophthalmic Genet       Date:  2011-03-29       Impact factor: 1.803

7.  An image-based biosensor assay strategy to screen for modulators of the microRNA 21 biogenesis pathway.

Authors:  David Shum; Bhavneet Bhinder; Constantin Radu; Thalia Farazi; Markus Landthaler; Thomas Tuschl; Paul Calder; Christina N Ramirez; Hakim Djaballah
Journal:  Comb Chem High Throughput Screen       Date:  2012-08       Impact factor: 1.339

8.  A high throughput scintillation proximity imaging assay for protein methyltransferases.

Authors:  Glorymar Ibanez; David Shum; Gil Blum; Bhavneet Bhinder; Constantin Radu; Christophe Antczak; Minkui Luo; Hakim Djaballah
Journal:  Comb Chem High Throughput Screen       Date:  2012-06-01       Impact factor: 1.339

9.  A high-content biosensor-based screen identifies cell-permeable activators and inhibitors of EGFR function: implications in drug discovery.

Authors:  Christophe Antczak; Jeni P Mahida; Bhavneet Bhinder; Paul A Calder; Hakim Djaballah
Journal:  J Biomol Screen       Date:  2012-05-09

10.  Modulators of the microRNA biogenesis pathway via arrayed lentiviral enabled RNAi screening for drug and biomarker discovery.

Authors:  David Shum; Bhavneet Bhinder; Hakim Djaballah
Journal:  Comb Chem High Throughput Screen       Date:  2013-12       Impact factor: 1.339

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  1 in total

Review 1.  Advances in Genomics for Drug Development.

Authors:  Roberto Spreafico; Leah B Soriaga; Johannes Grosse; Herbert W Virgin; Amalio Telenti
Journal:  Genes (Basel)       Date:  2020-08-15       Impact factor: 4.096

  1 in total

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