Development of a flow-cytometry-based method to measure the expression of cell surface molecules on endothelial cells is proposed for screening for novel regulators of inflammation. Many anti-inflammatory drugs, including corticosteroids, cyclooxygenase inhibitors and lipoxygenase inhibitors, inhibit the cytokine-dependent expression of certain endothelial cell surface molecules in culture. Our preliminary studies indicate that drugs can be distinguished based on their selective effects on particular cell surface molecules and/or under particular activation conditions. A robust assay system that can rapidly measure these effects under conditions that are more relevant to complex disease processes may be a useful tool for the rapid identification and characterization of novel anti-inflammatory drug compounds. The development of a multi-parameter flow cytometry method that allows the simultaneous measurement of multiple cell surface molecules in such a system may provide an innovative strategy for identifying and characterizing novel regulators of inflammation from synthetic or natural product libraries.

Proposed Commercial Applications

Commercial application: identifying anti-inflammatory drug compounds for pharmaceutical drug discovery.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
Project #
1R43AI048255-01A1
Application #
6341381
Study Section
Special Emphasis Panel (ZRG1-SSS-U (10))
Program Officer
Prograis, Lawrence J
Project Start
2001-04-15
Project End
2001-10-14
Budget Start
2001-04-15
Budget End
2001-10-14
Support Year
1
Fiscal Year
2001
Total Cost
$91,740
Indirect Cost
Name
Bioseek, Inc.
Department
Type
DUNS #
830570748
City
South San Francisco
State
CA
Country
United States
Zip Code
94080
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Kunkel, Eric J; Dea, Marlene; Ebens, Allen et al. (2004) An integrative biology approach for analysis of drug action in models of human vascular inflammation. FASEB J 18:1279-81
Kunkel, Eric J; Plavec, Ivan; Nguyen, Dat et al. (2004) Rapid structure-activity and selectivity analysis of kinase inhibitors by BioMAP analysis in complex human primary cell-based models. Assay Drug Dev Technol 2:431-41