This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Herpes simplex virus type 1 (HSV-1) infects approximately 90% of humans worldwide and during ocular infection produces inflammation and angiogenesis which can lead to blindness. In the United States, HSV infection is the leading cause of infection-induced blindness;nearly 40,000 new cases are reported, and 300,000 cases are treated yearly. Cyclin-dependent kinases, mostly known for their involvement in the cell cycle and transcription, are involved in herpesvirus transcription and replication. Cyclin-dependent kinase 9 (CDK9) and its downstream target, serine 2 phosphorylated RNA polymerase II, are essential in HSV-1 transcription. To date there is little literature on the role of cyclin-dependent kinases in herpesvirus infection of the eye or on the efficacy of CDK inhibitors in preventing HSV-1 associated ocular neovascularization and its consequences. During this funding period, we will begin to test the hypothesis that inhibitors of Cdk9 (flavopiridol, 5,6-dichlorobenzimidazole 1-?-D-ribofuranoside, and a dominant negative isoform of the kinase) decrease angiogenic signaling pathways upregulated by angiogenic factors in vitro. We will measure (1) cell survival, (2) cell proliferation, (3) cell migration, (4) cell invasion, and (5) tubule formation. Next, we will determine if inhibitors of Cdk9 decrease angiogenesis in the mouse eye model induced with HSV-1 infection, angiogenic factors, and mechanical stimulation. We have generated preliminary data suggesting that Cdk9 is required for angiogenesis induced by the Kaposi sarcoma Herpesvirus (KSHV) viral G protein-coupled receptor (vGPCR) or induced by a combination of angiogenic factors such as basic Fibroblast Growth Factor (bFGF) and Vascular Endothelial Growth Factor (VEGF).

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
5P20RR016456-10
Application #
8360373
Study Section
Special Emphasis Panel (ZRR1-RI-7 (01))
Project Start
2011-05-01
Project End
2012-04-30
Budget Start
2011-05-01
Budget End
2012-04-30
Support Year
10
Fiscal Year
2011
Total Cost
$54,686
Indirect Cost
Name
Louisiana State University A&M Col Baton Rouge
Department
Pathology
Type
Schools of Veterinary Medicine
DUNS #
075050765
City
Baton Rouge
State
LA
Country
United States
Zip Code
70803
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