Saturday, May 18, 2024 5/18/2024

Carbohydrate-Mediated Platelet Clearance

Award Number: R01HL089224
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By Issue Date FY or Funding FY:

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Project Summary The human body produces and removes 1011 platelets daily to maintain a normal steady-state platelet count. Production can be greatly increased under conditions of platelet destruction. We provided the first evidence that survival of platelets is intimately tied to surface glycans, and have shown that platelets with impaired Siaa2-3Galß1-4GlcNAc structures are removed in the liver by Kupffer cells and hepatocytes. Our data also showed that binding of desialylated platelets, i.e. platelets bearing terminal Galß1-4GlcNAc (LacNAc) structures, to the hepatocyte-specific Ashwell-Morell Receptor (AMR) increases thrombopoietin (TPO) production via JAK2-STAT3 signaling in hepatocytes. Thus the data suggest that desialylated platelet function as direct communicators between the bone marrow (BM) and hepatocytes. Here, we continue to investigate the platelet-hepatocyte-BM communication mechanism and the hypothesis that systemic signals altered in the absence of AMR regulate BM homeostasis will be solidified. We will identify novel systemic factors and decipher the mechanisms by which these factors regulate the BM hematopoietic niche. Our current data implicates a novel role of platelets as a regulator of BM vascular and mesenchymal cells, thereby affecting hematopoiesis via hepatocyte-secreted factor NRG4, the specific ErbB4 ligand. Recent genome wide association studies (GWAS) give credence to our preliminary data: Single-nucleotide polymorphisms (SNPs) in NRG4 and NRG3 genes have been associated with changes in peripheral red blood cell (RBC) and platelet count. We propose to investigate BM vascular, perivascular and mesenchymal progenitor cell populations and HSC function in the absence of AMR-mediated platelet clearance. Platelet surface glycans will be measured in platelets and plasma from individuals with SNP in NRG3/4 (Aim 1); and determine the molecular mechanisms by which NRG4 and ErbB4 regulate the HSC niche in the absence of hepatic AMR-mediated platelet clearance (Aim 2).


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: 2024 ( Subtotal = $521,930 )
2024	2024	VERSITI WISCONSIN, INC.	638 N 18TH ST	MILWAUKEE	WI	53233	MILWAUKEE	USA	Blood Diseases and Resources Research	000	16	1/23/2024	NON-COMPETING CONTINUATION	$521,930
														Subtotal = $521,930

Issue Date FY: 2023 ( Subtotal = $516,972 )
2023	2023	VERSITI WISCONSIN, INC.	638 N 18TH ST	MILWAUKEE	WI	53233	MILWAUKEE	USA	Blood Diseases and Resources Research	000	15	1/16/2023	COMPETING CONTINUATION	$516,972
														Subtotal = $516,972

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2020	VERSITI WISCONSIN, INC.	638 N 18TH ST	MILWAUKEE	WI	53233	MILWAUKEE	USA	Blood Diseases and Resources Research	001	14	11/24/2021	SUPPLEMENT FOR EXPANSION	$0
2022	2020	VERSITI WISCONSIN, INC.	638 N 18TH ST	MILWAUKEE	WI	53233	MILWAUKEE	USA	Blood Diseases and Resources Research	000	14	11/22/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $1,131,900 )
2020	2020	VERSITI WISCONSIN, INC.	638 N 18TH ST	MILWAUKEE	WI	53233	MILWAUKEE	USA	Blood Diseases and Resources Research	002	14	8/6/2020	SUPPLEMENT FOR EXPANSION	$495,000
2020	2020	VERSITI WISCONSIN, INC.	638 N 18TH ST	MILWAUKEE	WI	53233	MILWAUKEE	USA	Blood Diseases and Resources Research	000	14	5/14/2020	NON-COMPETING CONTINUATION	$636,900
2020	2020	VERSITI WISCONSIN, INC.	638 N 18TH ST	MILWAUKEE	WI	53233	MILWAUKEE	USA	Blood Diseases and Resources Research	001	14	8/6/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,131,900

Issue Date FY: 2019 ( Subtotal = $723,928 )
2019	2019	VERSITI WISCONSIN, INC.	638 N 18TH ST	MILWAUKEE	WI	53233	MILWAUKEE	USA	Blood Diseases and Resources Research	000	13	5/22/2019	NON-COMPETING CONTINUATION	$654,455
2019	2017	VERSITI WISCONSIN, INC.	638 N 18TH ST	MILWAUKEE	WI	53233	MILWAUKEE	USA	Blood Diseases and Resources Research	001	11	9/3/2019	COMPETING CONTINUATION	$69,473
														Subtotal = $723,928

Issue Date FY: 2018 ( Subtotal = $562,019 )
2018	2018	BLOODCENTER OF WISCONSIN, INC.	638 N 18TH ST	MILWAUKEE	WI	53233	MILWAUKEE	USA	Blood Diseases and Resources Research	001	12	5/10/2018	NON-COMPETING CONTINUATION	$631,492
2018	2016	BLOODCENTER OF WISCONSIN, INC.	638 N 18TH ST	MILWAUKEE	WI	53233	MILWAUKEE	USA	Blood Diseases and Resources Research	000	10	1/8/2018	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$69,473
														Subtotal = $562,019

Issue Date FY: 2017 ( Subtotal = $618,132 )
2017	2017	BLOODCENTER OF WISCONSIN, INC.	638 N 18TH ST	MILWAUKEE	WI	53233	MILWAUKEE	USA	Blood Diseases and Resources Research	006	11	8/23/2017	COMPETING CONTINUATION	$0
2017	2017	BLOODCENTER OF WISCONSIN, INC.	638 N 18TH ST	MILWAUKEE	WI	53233	MILWAUKEE	USA	Blood Diseases and Resources Research	005	11	7/24/2017	COMPETING CONTINUATION	$618,132
2017	2016	BLOODCENTER OF WISCONSIN, INC.	638 N 18TH ST	MILWAUKEE	WI	53233	MILWAUKEE	USA	Blood Diseases and Resources Research	004	10	7/21/2017	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2017	2016	BLOODCENTER OF WISCONSIN, INC.	638 N 18TH ST	MILWAUKEE	WI	53233	MILWAUKEE	USA	Blood Diseases and Resources Research	001	10	2/28/2017	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$319,500
2017	2016	BLOODCENTER OF WISCONSIN, INC.	638 N 18TH ST	MILWAUKEE	WI	53233	MILWAUKEE	USA	Blood Diseases and Resources Research	003	10	5/26/2017	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$26,203
2017	2016	BRIGHAM AND WOMEN'S HOSPITAL, INC., THE	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Blood Diseases and Resources Research	000	9	2/27/2017	EXTENSION WITH OR WITHOUT FUNDS	-$319,500
2017	2016	BRIGHAM AND WOMEN'S HOSPITAL, INC., THE	75 FRANCIS ST	BOSTON	MA	02115	SUFFOLK	USA	Blood Diseases and Resources Research	002	9	5/26/2017	EXTENSION WITH OR WITHOUT FUNDS	-$26,203
														Subtotal = $618,132

Issue Date FY: 2016 ( Subtotal = $420,500 )
2016	2016	BRIGHAM & WOMEN`S HOSPITAL	10 VINING STREET	BOSTON	MA	02115	SUFFOLK	USA	Blood Diseases and Resources Research	000	9	3/1/2016	EXTENSION WITH OR WITHOUT FUNDS	$420,500
														Subtotal = $420,500

Issue Date FY: 2015 ( Subtotal = $413,650 )
2015	2015	BRIGHAM & WOMEN`S HOSPITAL	10 VINING STREET	BOSTON	MA	02115	SUFFOLK	USA	Blood Diseases and Resources Research	000	8	3/17/2015	NON-COMPETING CONTINUATION	$413,650
														Subtotal = $413,650

Issue Date FY: 2014 ( Subtotal = $410,473 )
2014	2014	BRIGHAM & WOMEN`S HOSPITAL	10 VINING STREET	BOSTON	MA	02115	SUFFOLK	USA	Blood Diseases and Resources Research	000	7	3/21/2014	NON-COMPETING CONTINUATION	$410,473
														Subtotal = $410,473

Issue Date FY: 2013 ( Subtotal = $397,698 )
2013	2013	BRIGHAM & WOMEN`S HOSPITAL	10 VINING STREET	BOSTON	MA	02115	SUFFOLK	USA	Blood Diseases and Resources Research	001	6	4/1/2013	COMPETING CONTINUATION	$375,975
2013	2013	BRIGHAM & WOMEN`S HOSPITAL	10 VINING STREET	BOSTON	MA	02115	SUFFOLK	USA	Blood Diseases and Resources Research	002	6	7/3/2013	COMPETING CONTINUATION	$21,723
2013	2011	BRIGHAM & WOMEN`S HOSPITAL	10 VINING STREET	BOSTON	MA	02115	SUFFOLK	USA	Blood Diseases and Resources Research	000	5	3/29/2013	NON-COMPETING CONTINUATION	$0
														Subtotal = $397,698

Issue Date FY: 2011 ( Subtotal = $410,264 )
2011	2011	BRIGHAM & WOMEN`S HOSPITAL	10 VINING STREET	BOSTON	MA	02115	SUFFOLK	USA	Blood Diseases and Resources Research	000	5	6/15/2011	NON-COMPETING CONTINUATION	$410,264
														Subtotal = $410,264

Issue Date FY: 2010 ( Subtotal = $411,057 )
2010	2010	BRIGHAM & WOMEN'S HOSPITAL	10 VINING STREET	BOSTON	MA	02115	SUFFOLK	USA	Blood Diseases and Resources Research	000	4	6/30/2010	NON-COMPETING CONTINUATION	$411,057
														Subtotal = $411,057

Issue Date FY: 2009 ( Subtotal = $686,772 )
2009	2009	BRIGHAM & WOMEN'S HOSPITAL	10 VINING STREET	BOSTON	MA	02115	SUFFOLK	USA	Trans-NIH Recovery Act Research Support	001	3	7/30/2009	SUPPLEMENT FOR EXPANSION	$274,944
2009	2009	BRIGHAM & WOMEN'S HOSPITAL	10 VINING STREET	BOSTON	MA	02115	SUFFOLK	USA	Blood Diseases and Resources Research	000	3	6/26/2009	NON-COMPETING CONTINUATION	$411,828
														Subtotal = $686,772

Issue Date FY: 2008 ( Subtotal = $412,575 )
2008	2008	BRIGHAM & WOMEN'S HOSPITAL	10 VINING STREET	BOSTON	MA	02115	SUFFOLK	USA	Blood Diseases and Resources Research	000	2	7/2/2008	NON-COMPETING CONTINUATION	$412,575
														Subtotal = $412,575

Issue Date FY: 2007 ( Subtotal = $413,301 )
2007	2007	BRIGHAM & WOMEN'S HOSPITAL	10 VINING STREET	BOSTON	MA	02115	SUFFOLK	USA	Blood Diseases and Resources Research	000	1	9/4/2007	NEW	$413,301
														Subtotal = $413,301

Grand Total All Awards = $8,051,171

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Carbohydrate-Mediated Platelet Clearance

Award Number: R01HL089224

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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