The production of superoxide by the NADPH oxidase of neutrophils is essential for host defense against pathogens. Oxidase activation must be tightly regulated spatially and temporally to ensure efficient killing of pathogens without damage to host tissues. The p47phox subunit of the NADPH oxidase is critical for oxidase function, since its genetic absence results in the human disease Chronic Granulomatous Disease. The molecular details of how p47phox functions in oxidase activation and localization, however, are largely unknown. I hypothesize that specific domains and sequence motifs within p47phox coordinate the temporal and spatial regulation of the NADPH oxidase by controlling the interaction of p47phox with other oxidase components, and with specific structural and signal transduction molecules within neutrophils. In this manner, p47phox serves as a molecular integrator of protein- and lipid kinase-mediated signaling events within neutrophils.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32AI054091-02
Application #
6921411
Study Section
Special Emphasis Panel (ZRG1-F07 (20))
Program Officer
Prograis, Lawrence J
Project Start
2003-08-15
Project End
2006-08-14
Budget Start
2004-08-15
Budget End
2005-08-14
Support Year
2
Fiscal Year
2004
Total Cost
$47,296
Indirect Cost
Name
Massachusetts Institute of Technology
Department
Internal Medicine/Medicine
Type
Schools of Arts and Sciences
DUNS #
001425594
City
Cambridge
State
MA
Country
United States
Zip Code
02139