The Columbia Center in the MLSCN will be differentiated on the basis of its strength and experience in cell biology, high content/high resolution automated cellular imaging and image analysis, and phenotypic assay design and implementation. Building on these existing strengths, our Center proposes a strategic focus on high throughput screening using phenotypic assays at the cellular and subcellular levels to identify bioactive compounds, which will enable us to meet or exceed the screening milestones mandated in the RFA within the scope of the allowed budget. Because of its strategic differentiation, the Columbia Center will perform uniquely within and to the benefit of the MLSCN network as a whole. Sister centers in the network which screen against defined molecular targets will dynamically interact with Columbia for secondary screening services. To facilitate this and to add value, the Columbia Center will draw on the assays it implements for referring investigators to create a """"""""house repertoire"""""""" of biological assays. Profiling of hits against this repertoire of biology will provide important information on specificity at the biological level to complement information on the compound's selectivity at the protein/target level. This kind of information will be critical for the network to achieve best practice by focusing what will be limiting chemistry resources on the most promising hits. To accomplish the above goals in three years, the Columbia Center will be structured internally as a series of five functional components (assay implementation, HTS, probe development, informatics, management) each with defined goals, milestones and timelines. Each function will be led by a dedicated senior scientist, and the project will be coordinated by a dedicated project manager: The project is strongly supported by Columbia, which has already purchased a state-of-the-art highthroughput confocal cell imaging system (GE INCell3000) for the project, and will provide space (approx 5,000 nsf) adjacent to the PI's laboratory as well capital equipment needed to allow full automation of cellular screening at the Center.

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54HG003914-02
Application #
7312418
Study Section
Special Emphasis Panel (ZMH1)
Project Start
Project End
Budget Start
2006-07-01
Budget End
2007-06-30
Support Year
2
Fiscal Year
2006
Total Cost
$2,869,244
Indirect Cost
Name
Columbia University (N.Y.)
Department
Type
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
Vang, Torkel; Xie, Yuli; Liu, Wallace H et al. (2011) Inhibition of lymphoid tyrosine phosphatase by benzofuran salicylic acids. J Med Chem 54:562-71
Vidovi?, Dušica; Xie, Yuli; Rinderspacher, Alison et al. (2011) Distinct functional and conformational states of the human lymphoid tyrosine phosphatase catalytic domain can be targeted by choice of the inhibitor chemotype. J Comput Aided Mol Des 25:873-83
Vidovi?, Dusica; Schürer, Stephan C (2009) Knowledge-based characterization of similarity relationships in the human protein-tyrosine phosphatase family for rational inhibitor design. J Med Chem 52:6649-59
Rinderspacher, Alison; Cremona, Maria Laura; Liu, Yidong et al. (2009) Potent inhibitors of Huntingtin protein aggregation in a cell-based assay. Bioorg Med Chem Lett 19:1715-7
Xie, Yuli; Liu, Yidong; Gong, Gangli et al. (2009) Discovery of potent non-urea inhibitors of soluble epoxide hydrolase. Bioorg Med Chem Lett 19:2354-9
Xie, Yuli; Liu, Yidong; Gong, Gangli et al. (2008) Discovery of a novel submicromolar inhibitor of the lymphoid specific tyrosine phosphatase. Bioorg Med Chem Lett 18:2840-4
Mayer, Thomas; Jagla, Bernd; Wyler, Michael R et al. (2006) Cell-based assays using primary endothelial cells to study multiple steps in inflammation. Methods Enzymol 414:266-83