In 2002, in response to the NIH Roadmap to Molecular Libraries and Imaging, we conceived the process and now have fully established a P50 High Throughput Screening Robotics Core. The new Core represents a multi-departmental effort with fiscal support for establishing the Core coming from P50 funds in combination with the Department of Radiology, Department of Molecular Biology & Pharmacology, and Department of Cell Biology as well as the Howard Hughes Medical Institute. The Dean of Washington University School of Medicine as well as the Director of the Washington University Siteman Cancer Center joined our effort with the commitment of additional funds for further development of the resource. Overall, nearly $2M has been invested in the establishment of this resource. This Core serves as an outstanding on-going example of how our P50 program has leveraged university resources and continues to stimulate interdisciplinary molecular imaging activity throughout the WU campus. Functionally and symbolically, Drs. Helen Piwnica-Worms (Cell Biology), Rafi Kopan (Molecular Biology &Pharmacology), and David Piwnica-Worms (Radiology ) serve as Core Co-Directors with shared administration and scientific oversight of Core activities. This Core is housed in the McDonnell Sciences Building, Room 316, across the street from the East Building Imaging Annex, site of many of the Molecular Imaging Center collaborative activities. Construction of the room and instrument requirements was finished in 2005 and installations of the Beckman Coulter BioMek FX liquid handler as well as an ORCA robot on a 6 ft rail were completed in the summer/fall of 2005. A bio-barrier entryway was constructed and positive-pressure, HEPA filtered air circulation has been installed. Integrated readout and cell culture stations are included with the imaging and analysis instruments. This innovative Core was founded on molecular imaging platforms for readout of a wide range of bio-assays and underpins three of the Research Projects in this application. This Core assures that the personnel and resources for high throughput screening are available to all our ICMIC investigators. Jayne Marasa, senior Core lab manager, directs day-to-day experiments and has optimized several protocols and logistical requirements for our first projects in high throughput screening. Exciting data are now coming on-line during the summer 2006. The Core allows for automated screening of cells cultured in 96 or 384 plate formats and can be applied to multiple investigator-initiated molecular imaging applications arising from P50 investigators and throughout the university community. The applications include: 1) small molecule screens applied to cells engineered by WU investigators for imaging and therapeutic drug leads. 2) small molecule or peptide screens to identify enzyme inhibitors (directed against high priority proteases, kinases, phosphatases, etc.) or modulators of protein-protein interactions. 3) genome-wide siRNA library screens against kinases, phosphatases and E3-ligases in human cells targeting signal transduction, cell growth or cell death responses.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
5P50CA094056-11
Application #
8233028
Study Section
Special Emphasis Panel (ZCA1)
Project Start
Project End
Budget Start
2011-01-01
Budget End
2011-12-31
Support Year
11
Fiscal Year
2011
Total Cost
$220,214
Indirect Cost
Name
Washington University
Department
Type
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Pisaneschi, Federica; Kelderhouse, Lindsay E; Hardy, Amanda et al. (2017) Automated, Resin-Based Method to Enhance the Specific Activity of Fluorine-18 Clicked PET Radiotracers. Bioconjug Chem 28:583-589
Zhu, Zhe; Gorman, Matthew J; McKenzie, Lisa D et al. (2017) Zika virus has oncolytic activity against glioblastoma stem cells. J Exp Med 214:2843-2857
Zhang, Daoxiang; Li, Lin; Jiang, Hongmei et al. (2017) Constitutive IRAK4 Activation Underlies Poor Prognosis and Chemoresistance in Pancreatic Ductal Adenocarcinoma. Clin Cancer Res 23:1748-1759
Lu, Zhi Hong; Kaliberov, Sergey; Sohn, Rebecca E et al. (2017) A new model of multi-visceral and bone metastatic prostate cancer with perivascular niche targeting by a novel endothelial specific adenoviral vector. Oncotarget 8:12272-12289
Miller, Jessica; Wang, Steven T; Orukari, Inema et al. (2017) Perfusion-based fluorescence imaging method delineates diverse organs and identifies multifocal tumors using generic near-infrared molecular probes. J Biophotonics :
Miller, Jessica P; Habimana-Griffin, LeMoyne; Edwards, Tracy S et al. (2017) Multimodal fluorescence molecular imaging for in vivo characterization of skin cancer using endogenous and exogenous fluorophores. J Biomed Opt 22:66007
Zacharias, Niki Marie; McCullough, Christopher; Shanmugavelandy, Sriram et al. (2017) Metabolic Differences in Glutamine Utilization Lead to Metabolic Vulnerabilities in Prostate Cancer. Sci Rep 7:16159
Gilson, Rebecca C; Black, Kvar C L; Lane, Daniel D et al. (2017) Hybrid TiO2 -Ruthenium Nano-photosensitizer Synergistically Produces Reactive Oxygen Species in both Hypoxic and Normoxic Conditions. Angew Chem Int Ed Engl 56:10717-10720
Tang, Rui; Habimana-Griffin, LeMoyne M; Lane, Daniel D et al. (2017) Nanophotosensitive drugs for light-based cancer therapy: what does the future hold? Nanomedicine (Lond) 12:1101-1105
Miller, Jessica P; Maji, Dolonchampa; Lam, Jesse et al. (2017) Noninvasive depth estimation using tissue optical properties and a dual-wavelength fluorescent molecular probe in vivo. Biomed Opt Express 8:3095-3109

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