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Role of SHIP in NK Cell Biology

Award Number: R01HL072523
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2002
PERIOD OF PERFORMANCE END DATE: 06/30/2011

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Role of SHIP in NK Cell Biology - DESCRIPTION (provided by applicant): Over the last four years this grant has enabled us to make several novel advances including the demonstration that the SH2-containing Inositol Phosphatase (SHIP) plays a pivotal role in the biology of NK cells, Graft-Versus-Host Disease (GvHD) and rejection of allogeneic bone marrow (BM) grafts.(1-5) We find that the NK receptor repertoire (NKRR) of SHIP mice is highly disrupted with certain NK receptors (NKR) dominating the repertoire of SHIP-/- NK cells. Moreover the subset of receptors that becomes dominant in SHIP-/- NK cells can vary with allelic differences in self ligands such as MHC class I. The "receptor dominance" created by SHIP-deficiency in turn compromises cytolytic function suggesting a novel mechanism for NK dysfunction and immune deficiency. In aggregate our studies indicate SHIP regulates NKR signaling pathways that sense self ligands and that SHIP'S role is to prevent one or a few NK NKR from dominating the NKRR.(1,4,5) We hypothesize then that SHIP regulates the NKRR through signaling pathways that control survival and proliferation of NK cell subsets (indirect effects) or NKR expression (direct effects). Based on our progress to date this revised renewal application has been restructured as three aims. In Aims 1 and 2 we will define in molecular terms the signaling pathways and components of SHIP required for regulation of the murine NKRR. The revised Aim 3 has been refocused to define in molecular terms why key NK cytolytic functions are altered by SHIP-deficiency. This renewal application will be pursued in the following specific aims: Aim 1: Define self-ligand/receptor pairs, and signaling proteins recruited to them, required for regulation of the NKRR by SHIP. Aim 2: Define effector pathways altered by SHIP-deficiency that lead to NKRR disruption. Aim 3: Define the mechanisms responsible for compromised function of SHIP-/- NK cells.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2017 ( Subtotal = -$1,564 )
2017	2014	RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, THE	750 E ADAMS ST	SYRACUSE	NY	13210	ONONDAGA	USA	Blood Diseases and Resources Research	000	12	11/23/2016	NON-COMPETING CONTINUATION	-$1,564
														Subtotal = -$1,564

Issue Date FY: 2014 ( Subtotal = $275,952 )
2014	2014	RESEARCH FOUNDATION OF STATE UNIV OF NEW YORK (SUNY)	P.O. BOX 9	ALBANY	NY	12201	ALBANY	USA	Blood Diseases and Resources Research	000	12	6/27/2014	NON-COMPETING CONTINUATION	$275,952
														Subtotal = $275,952

Issue Date FY: 2013 ( Subtotal = $268,067 )
2013	2013	RESEARCH FOUNDATION OF STATE UNIV OF NEW YORK (SUNY)	P.O. BOX 9	ALBANY	NY	12201	ALBANY	USA	Blood Diseases and Resources Research	000	11	7/9/2013	NON-COMPETING CONTINUATION	$268,067
														Subtotal = $268,067

Issue Date FY: 2012 ( Subtotal = $281,583 )
2012	2012	RESEARCH FOUNDATION OF STATE UNIV OF NEW YORK (SUNY)	P.O. BOX 9	ALBANY	NY	12201	ALBANY	USA	Blood Diseases and Resources Research	000	10	6/25/2012	NON-COMPETING CONTINUATION	$281,583
														Subtotal = $281,583

Issue Date FY: 2011 ( Subtotal = $422,367 )
2011	2011	RESEARCH FOUNDATION OF STATE UNIV OF NEW YORK (SUNY)	P.O. BOX 9	ALBANY	NY	12201	ALBANY	USA	Blood Diseases and Resources Research	001	9	8/1/2011	COMPETING CONTINUATION	$422,367
2011	2010	UNIVERSITY HOSPITAL OF UPSTATE MEDICAL CENTER	750 EAST ADAMS STREET	SYRACUSE	NY	13210	ONONDAGA	USA	Blood Diseases and Resources Research	000	8	8/1/2011	NON-COMPETING CONTINUATION	$0
														Subtotal = $422,367

Issue Date FY: 2010 ( Subtotal = $392,500 )
2010	2010	UNIVERSITY HOSPITAL OF UPSTATE MEDICAL CENTER	750 EAST ADAMS STREET	SYRACUSE	NY	13210	ONONDAGA	USA	Blood Diseases and Resources Research	000	8	7/8/2010	NON-COMPETING CONTINUATION	$392,500
														Subtotal = $392,500

Issue Date FY: 2009 ( Subtotal = $406,750 )
2009	2009	UNIVERSITY HOSPITAL OF UPSTATE MEDICAL CENTER	750 EAST ADAMS STREET	SYRACUSE	NY	13210	ONONDAGA	USA	Blood Diseases and Resources Research	001	7	8/28/2009	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$406,750
2009	2008	H LEE MOFFITT CANCER CENTER & RESEARCH INSTITUTE	12902 MAGNOLIA DRIVE	TAMPA	FL	33612	HILLSBOROUGH	USA	Blood Diseases and Resources Research	000	6	8/28/2009	NON-COMPETING CONTINUATION	$0
														Subtotal = $406,750

Issue Date FY: 2008 ( Subtotal = $410,500 )
2008	2008	H LEE MOFFITT CANCER CENTER & RESEARCH INSTITUTE	12902 MAGNOLIA DRIVE	TAMPA	FL	33612	HILLSBOROUGH	USA	Blood Diseases and Resources Research	000	6	7/2/2008	NON-COMPETING CONTINUATION	$410,500
														Subtotal = $410,500

Issue Date FY: 2007 ( Subtotal = $427,000 )
2007	2007	H LEE MOFFITT CANCER CENTER & RESEARCH INSTITUTE	12902 MAGNOLIA DRIVE	TAMPA	FL	33612	HILLSBOROUGH	USA	Blood Diseases and Resources Research	000	5	7/23/2007	COMPETING CONTINUATION	$427,000
														Subtotal = $427,000

Issue Date FY: 2005 ( Subtotal = $406,516 )
2005	2005	UNIVERSITY OF SOUTH FLORIDA	4202 E FOWLER AVENUE	TAMPA	FL	33620	HILLSBOROUGH	USA	Blood Diseases and Resources Research	000	4	7/27/2005	NON-COMPETING CONTINUATION	$406,516
														Subtotal = $406,516

Issue Date FY: 2004 ( Subtotal = $463,523 )
2004	2004	UNIVERSITY OF SOUTH FLORIDA	4202 E FOWLER AVENUE	TAMPA	FL	33620	HILLSBOROUGH	USA	Blood Diseases and Resources Research	001	2	3/29/2004	SUPPLEMENT FOR EXPANSION	$57,007
2004	2004	UNIVERSITY OF SOUTH FLORIDA	4202 E FOWLER AVENUE	TAMPA	FL	33620	HILLSBOROUGH	USA	Blood Diseases and Resources Research	000	3	6/18/2004	NON-COMPETING CONTINUATION	$406,516
														Subtotal = $463,523

Issue Date FY: 2003 ( Subtotal = $290,000 )
2003	2003	UNIVERSITY OF SOUTH FLORIDA	4202 E FOWLER AVENUE	TAMPA	FL	33620	HILLSBOROUGH	USA	Blood Diseases and Resources Research	000	2	6/18/2003	NON-COMPETING CONTINUATION	$290,000
														Subtotal = $290,000

Issue Date FY: 2002 ( Subtotal = $290,000 )
2002	2002	UNIVERSITY OF SOUTH FLORIDA	4202 E FOWLER AVENUE	TAMPA	FL	33620	HILLSBOROUGH	USA	Blood Diseases and Resources Research	000	1	6/24/2002	NEW	$290,000
														Subtotal = $290,000

Grand Total All Awards = $4,333,194

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Role of SHIP in NK Cell Biology

Award Number: R01HL072523

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 07/01/2002

PERIOD OF PERFORMANCE END DATE: 06/30/2011

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