Thursday, November 21, 2024 11/21/2024

Fibrin(ogen) Structure and Interactions

Award Number: R01HL056051
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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PROJECT SUMMARY Fibrinogen is a multifunctional plasma protein that, after conversion into polymeric fibrin, promotes hemostasis and plays a pivotal role in various physiological and pathological processes, including wound healing, thrombosis, atherogenesis, tumorigenesis, and more. Inflammation and angiogenesis are integral parts of wound healing; however, in pathological settings, these two processes contribute to the development of inflammation-related cardiovascular diseases and the progression of tumor growth and metastasis. Our previous studies primarily focused on the newly discovered fibrin-VLDL receptor-dependent inflammatory pathway, which promotes the transendothelial migration of leukocytes and, consequently, inflammation. In these studies, we established the molecular mechanism underlying this pathway and hypothesized that the fibrin-derived β15-42 fragment, which was shown to exhibit significant protective effects in numerous inflammation-related animal models, inhibits this pathway by interacting with a putative receptor. Recently, we discovered that endothelial N-cadherin is a novel receptor for fibrin. Our extensive preliminary data suggest that N-cadherin is a putative receptor for β15-42, and the interaction of fibrin with this receptor promotes angiogenesis. Based on these data and our previous findings, we propose to characterize the novel fibrin-(N-cadherin) interaction and establish its role in fibrin-dependent inflammation and angiogenesis. Specifically, we aim to establish the structural basis for the fibrin-(N-cadherin) interaction (Specific Aim 1), test our hypothesis that N-cadherin is a putative receptor for the β15-42 fragment, whose interaction with this receptor inhibits leukocyte transmigration (Specific Aim 2), and test our hypothesis that fibrin-(N-cadherin) interaction triggers fibrin-dependent angiogenesis (Specific Aim 3). Additionally, we intend to design novel, efficient inhibitors of the fibrin-(N-cadherin) interaction with potent anti-inflammatory and anti-angiogenic properties. These inhibitors may be developed as potential therapeutics for treating fibrin-dependent inflammatory disorders and angiogenesis-related tumorigenesis.


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: 2025 ( Subtotal = $0 )
2025	2024	UNIVERSITY OF MARYLAND, BALTIMORE	220 ARCH ST OFC LEVEL2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Blood Diseases and Resources Research	000	22	10/18/2024	COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $595,327 )
2024	2024	UNIVERSITY OF MARYLAND, BALTIMORE	220 ARCH ST OFC LEVEL2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Blood Diseases and Resources Research	001	22	8/6/2024	COMPETING CONTINUATION	$595,327
2024	2021	UNIVERSITY OF MARYLAND, BALTIMORE	220 ARCH ST OFC LEVEL2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Blood Diseases and Resources Research	000	21	7/16/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $595,327

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2021	UNIVERSITY OF MARYLAND, BALTIMORE	220 ARCH ST OFC LEVEL2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Blood Diseases and Resources Research	000	21	6/1/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $460,850 )
2021	2021	UNIVERSITY OF MARYLAND	220 ARCH ST RM 02148	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Blood Diseases and Resources Research	000	21	6/4/2021	NON-COMPETING CONTINUATION	$460,850
														Subtotal = $460,850

Issue Date FY: 2020 ( Subtotal = $460,850 )
2020	2020	UNIVERSITY OF MARYLAND	220 ARCH ST RM 02148	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Blood Diseases and Resources Research	000	20	5/19/2020	NON-COMPETING CONTINUATION	$460,850
														Subtotal = $460,850

Issue Date FY: 2019 ( Subtotal = $446,945 )
2019	2019	UNIVERSITY OF MARYLAND	220 ARCH ST RM 02148	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Blood Diseases and Resources Research	000	19	6/12/2019	NON-COMPETING CONTINUATION	$446,945
														Subtotal = $446,945

Issue Date FY: 2018 ( Subtotal = $446,945 )
2018	2018	UNIVERSITY OF MARYLAND	220 ARCH ST RM 02148	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Blood Diseases and Resources Research	000	18	5/29/2018	COMPETING CONTINUATION	$446,945
2018	2016	UNIVERSITY OF MARYLAND	220 ARCH ST RM 02148	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Blood Diseases and Resources Research	001	17	9/7/2018	EXTENSION WITH OR WITHOUT FUNDS	$0
														Subtotal = $446,945

Issue Date FY: 2016 ( Subtotal = $395,263 )
2016	2016	UNIVERSITY OF MARYLAND BALTIMORE PROFESSIONAL SCHOOLS	220 ARCH ST OFFICE LEVEL 2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Blood Diseases and Resources Research	000	17	5/31/2016	EXTENSION WITH OR WITHOUT FUNDS	$395,263
														Subtotal = $395,263

Issue Date FY: 2015 ( Subtotal = $389,333 )
2015	2015	UNIVERSITY OF MARYLAND BALTIMORE PROFESSIONAL SCHOOLS	220 ARCH ST OFFICE LEVEL 2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Blood Diseases and Resources Research	000	16	4/30/2015	NON-COMPETING CONTINUATION	$389,333
														Subtotal = $389,333

Issue Date FY: 2014 ( Subtotal = $387,357 )
2014	2014	UNIVERSITY OF MARYLAND BALTIMORE PROFESSIONAL SCHOOLS	220 ARCH ST OFFICE LEVEL 2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Blood Diseases and Resources Research	000	15	5/16/2014	NON-COMPETING CONTINUATION	$387,357
														Subtotal = $387,357

Issue Date FY: 2013 ( Subtotal = $376,288 )
2013	2013	UNIVERSITY OF MARYLAND BALTIMORE PROFESSIONAL SCHOOLS	220 ARCH ST OFFICE LEVEL 2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Blood Diseases and Resources Research	001	14	8/9/2013	COMPETING CONTINUATION	$376,288
2013	2011	UNIVERSITY OF MARYLAND BALTIMORE PROFESSIONAL SCHOOLS	220 ARCH ST OFFICE LEVEL 2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Blood Diseases and Resources Research	000	13	11/6/2012	NON-COMPETING CONTINUATION	$0
														Subtotal = $376,288

Issue Date FY: 2011 ( Subtotal = $375,000 )
2011	2011	UNIVERSITY OF MARYLAND BALTIMORE PROFESSIONAL SCHOOLS	220 ARCH ST OFFICE LEVEL 2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Blood Diseases and Resources Research	000	13	7/26/2011	NON-COMPETING CONTINUATION	$375,000
														Subtotal = $375,000

Issue Date FY: 2010 ( Subtotal = $375,000 )
2010	2010	UNIVERSITY OF MARYLAND BALTIMORE PROFESSIONAL SCHOOLS	220 ARCH ST OFFICE LEVEL 2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Blood Diseases and Resources Research	000	12	7/14/2010	NON-COMPETING CONTINUATION	$375,000
														Subtotal = $375,000

Issue Date FY: 2009 ( Subtotal = $375,000 )
2009	2009	UNIVERSITY OF MARYLAND BALTIMORE PROFESSIONAL SCHOOLS	220 ARCH ST OFFICE LEVEL 2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Blood Diseases and Resources Research	000	11	7/15/2009	NON-COMPETING CONTINUATION	$375,000
														Subtotal = $375,000

Issue Date FY: 2008 ( Subtotal = $375,000 )
2008	2008	UNIVERSITY OF MARYLAND BALTIMORE PROFESSIONAL SCHOOLS	220 ARCH ST OFFICE LEVEL 2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Blood Diseases and Resources Research	000	10	7/28/2008	COMPETING CONTINUATION	$375,000
														Subtotal = $375,000

Issue Date FY: 2006 ( Subtotal = $362,526 )
2006	2006	UNIVERSITY OF MARYLAND BALTIMORE PROFESSIONAL SCHOOLS	220 ARCH ST OFFICE LEVEL 2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Blood Diseases and Resources Research	000	9	6/16/2006	NON-COMPETING CONTINUATION	$362,526
														Subtotal = $362,526

Issue Date FY: 2005 ( Subtotal = $371,250 )
2005	2005	UNIVERSITY OF MARYLAND BALTIMORE PROFESSIONAL SCHOOLS	737 WEST LOMBARD STREET	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Blood Diseases and Resources Research	000	8	6/30/2005	NON-COMPETING CONTINUATION	$371,250
														Subtotal = $371,250

Issue Date FY: 2004 ( Subtotal = $371,250 )
2004	2004	UNIVERSITY OF MARYLAND BALTIMORE PROFESSIONAL SCHOOLS	737 WEST LOMBARD STREET	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Blood Diseases and Resources Research	000	7	7/23/2004	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$371,250
														Subtotal = $371,250

Issue Date FY: 2003 ( Subtotal = $385,500 )
2003	2003	AMERICAN NATIONAL RED CROSS HEADQUARTERS	600 A FOREST POINT CIRCLE	CHARLOTTE	NC	28273	MECKLENBURG	USA	Blood Diseases and Resources Research	000	6	8/4/2003	COMPETING CONTINUATION	$385,500
														Subtotal = $385,500

Issue Date FY: 2002 ( Subtotal = $326,692 )
2002	2002	AMERICAN NATIONAL RED CROSS HEADQUARTERS	600 A FOREST POINT CIRCLE	CHARLOTTE	NC	28273	MECKLENBURG	USA	Blood Diseases and Resources Research	000	5	12/24/2001	NON-COMPETING CONTINUATION	$326,692
														Subtotal = $326,692

Issue Date FY: 2001 ( Subtotal = $317,306 )
2001	2001	AMERICAN NATIONAL RED CROSS HEADQUARTERS	600 A FOREST POINT CIRCLE	CHARLOTTE	NC	28273	MECKLENBURG	USA	Blood Diseases and Resources Research	000	4	1/25/2001	NON-COMPETING CONTINUATION	$317,306
														Subtotal = $317,306

Issue Date FY: 2000 ( Subtotal = $308,195 )
2000	2000	AMERICAN NATIONAL RED CROSS HEADQUARTERS	600 A FOREST POINT CIRCLE	CHARLOTTE	NC	28273	MECKLENBURG	USA	Blood Diseases and Resources Research	000	3	12/15/1999	NON-COMPETING CONTINUATION	$308,195
														Subtotal = $308,195

Issue Date FY: 1999 ( Subtotal = $299,346 )
1999	1999	AMERICAN NATIONAL RED CROSS HEADQUARTERS	600 A FOREST POINT CIRCLE	CHARLOTTE	NC	28273	MECKLENBURG	USA	Blood Diseases and Resources Research	000	2	12/23/1998	NON-COMPETING CONTINUATION	$299,346
														Subtotal = $299,346

Issue Date FY: 1998 ( Subtotal = $290,756 ) (Continued on the next page)
Grand Total All Awards = $8,491,979

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Fibrin(ogen) Structure and Interactions

Award Number: R01HL056051

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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