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Abstract
Grant Number: 1R21NS053593-01 Project Title: Novel High Content Vascular Patterning Assay(RMI)
PI Information: Name Title MOHAN, ROYCE royce.mohan@uky.edu Abstract: DESCRIPTION (provided by applicant): Angiogenesis, the growth of new blood vessels, occurs in a diverse array of human diseases. Even though anti-angiogenesis remains a large market for Pharmaceuticals, high content high throughput cell based assays for angiogenesis inhibitor discovery remain to be developed for this application. It is our belief that developing new assays as screening tools for discovery of inhibitors that target endothelial cell differentiation can prove to be an efficient means of identifying new classes of anti-angiogenic drugs. Here we propose to develop a high content vascular patterning assay that can likely be adopted for high throughput screening (HTS). We plan to build a prototype of a powerful high content screening platform by interfacing high throughput screening capability with multiparameter optical imaging of endothelial cell patterning in three dimensional (3-D) matrices. Our innovative approach to achieve these goals will be accomplished through the following aims. In Specific aim 1 we will develop and validate a 3-D endothelial cell patterning assay (3-D ECPA). We will accomplish this by developing methods to generate highly robust multicellular endothelial cell spheroids on microcarrier beads and array the spheroids in 3-D collagen matrix in 384 well optical screening plates. In addition, these assays will be performed under hypoxic environment. In Specific Aim 2 we plan to develop and validate a high content (HC) image analysis platform for use with 3-D ECPA. This will be accomplished by developing software that identifies novel features of endothelial cell patterning in 3-D matrix and apply automated analysis to obtain morphogenic fingerprints. Finally, we will validate the 3-DECPA and image analysis software for HTS application by screening a diversity set of natural products. We believe that this HC-HTS platform will offer unique opportunities to screen vast numbers of small molecule inhibitors of angiogenesis and assist in drug discovery.
Public Health Relevance:
This Public Health Relevance is not available.Thesaurus Terms:
angiogenesis inhibitor, drug discovery /isolation, high throughput technology, technology /technique development
biomedical automation, image processing, vascular endothelium
bioassay, biotechnology, computer program /software, digital imaging, optics
Institution: UNIVERSITY OF KENTUCKY 109 KINKEAD HALL LEXINGTON, KY 405060057 Fiscal Year: 2005 Department: OPHTHALMOLOGY AND VISUAL SCIENCES Project Start: 30-SEP-2005 Project End: 31-AUG-2008 ICD: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE IRG: ZNS1