The proposed program project is based on our central hypothesis that Wiskott-Aldrich syndrome protein (WASP), its homologue N-WASP, and its partner WASP interactive protein (WIP), are involved in cytoskeletal re-organization and gene induction upon activation of blood cells. Toward this end we targeted the genes encoding all these proteins by homologous recombination. We plan to exploit these """"""""knock-outs"""""""" to elucidate the pathway(s) from cell surface receptors to cytoskeletal re-organization in T cells, B cells and platelets. The proposal consists of four projects and two cores. Project 1 (R. Geha) seeks to understand the overlapping and non-overlapping roles of WASP, WIP and the WASP-WIP complex in T cell activation and cytoskeletal reorganization. Project 2 (S. Snapper and F. Alt) and Project 3 (L. Notarangelo) will dissect the role of WASP, N-WASP and WIP in T and B cell function respectively. Project 4 (John Hartwig) will examine the role of WASP, N-WASP and WIP in maintaining platelet homeostasis. Core A will administer the program. Core B will provide genetically engineered mice and generate monoclonal antibodies for all four projects.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL059561-14
Application #
8122173
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Program Officer
Mitchell, Phyllis
Project Start
1997-09-30
Project End
2013-08-31
Budget Start
2011-09-01
Budget End
2012-08-31
Support Year
14
Fiscal Year
2011
Total Cost
$1,790,387
Indirect Cost
Name
Children's Hospital Boston
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02115
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Moran, Christopher J; Klein, Christoph; Muise, Aleixo M et al. (2015) Very early-onset inflammatory bowel disease: gaining insight through focused discovery. Inflamm Bowel Dis 21:1166-75
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