This application is designed to develop the principle investigator to become an independent physician scientist. To accomplish this goal the PI proposes a detailed program involving the dissection of several important molecular signaling pathways in macrophages. Dr. Alan Aderem, a leader in the field of macrophage biology and signaling, will mentor the PI through this program. The training program also includes specific course work, attendance at seminars, and the formation of a scientific advisory committee. The purpose of this proposal is to analyze the effect of the HMG-CoA reductase inhibitor simvastatin on the immune function of macrophages. Atherosclerosis is a chronic inflammatory disease and macrophages play a central role in all phases on the process including initiation, progression and the eventual acute complications. Macrophages coordinate the innate and specific immune system through their ability to phagocytose and clear pathogens and couple this to the release of inflammatory mediators. The HMG-CoA reductase inhibitors, or statins, are a class of drug designed to inhibit cholesterol synthesis that have been shown to dramatically reduce cardiovascular disease endpoints. However, their lipid lowering properties incompletely explain the beneficial effect of these drugs.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08HL071582-04
Application #
7010682
Study Section
Special Emphasis Panel (ZHL1-CSR-M (O1))
Program Officer
Commarato, Michael
Project Start
2003-02-03
Project End
2008-01-31
Budget Start
2006-02-01
Budget End
2007-01-31
Support Year
4
Fiscal Year
2006
Total Cost
$123,011
Indirect Cost
Name
Institute for Systems Biology
Department
Type
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98109
Liu, Zhanwei; Hu, Guoen; Wu, Guochang et al. (2008) Semi-orthogonal Frame Wavelets and Parseval Frame Wavelets Associated with GMRA. Chaos Solitons Fractals 38:1449-1456
Matsumoto, Makoto; Einhaus, Derek; Gold, Elizabeth S et al. (2004) Simvastatin augments lipopolysaccharide-induced proinflammatory responses in macrophages by differential regulation of the c-Fos and c-Jun transcription factors. J Immunol 172:7377-84
Gold, Elizabeth S; Simmons, Randi M; Petersen, Timothy W et al. (2004) Amphiphysin IIm is required for survival of Chlamydia pneumoniae in macrophages. J Exp Med 200:581-6