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INFORMATION SIGNALING PATHWAYS IN THE VASCULATURE

Award Number: P01HL054710
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/1997
PERIOD OF PERFORMANCE END DATE: 03/31/2012

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INFORMATION SIGNALING PATHWAYS IN THE VASCULATURE - DESCRIPTION (provided by applicant): Inflammatory pathways within the vasculature and at the blood brain barrier regulate the response of the vessel wall to injury. The unifying theme of this competitive program project renewal is that lipoprotein receptors (LRP1, LRP1B, and VLDLR) and the leukocyte and endothelial receptors integrin Mac-1 and VEcadherin modulate the inflammatory response in a cooperative fashion that is influenced by their ligands, tPA, PA1-1, and fibrin(ogen). The overall objective is to define molecular pathways by which LRP, Mac-1, tPA, PAI-1, and fibrin cooperate to modulate the inflammatory response during atherogenesis by regulating inflammatory cell migration and function to define mechanisms by which these molecules modulate the integrity of the blood brain barrier (BBB). These objectives will be achieved through the combined efforts of four principal investigators and three core facilities. Dr. Strickland (Project 1) will focus his research on the role of lipoprotein receptors in inflammation in the vessel wall. In collaboration with Dr. Zhang (Project 3) and Dr. Medved (Project 4), he will test the hypothesis that lipoprotein receptors, particularly LRP, regulate inflammatory processes by modulating the functional properties of integrins and their ability to interact with fibrin(ogen), thereby affecting macrophage migration. Using macrophage-specific LRP knockout mice, he will test the hypothesis that LRP participates in a novel signaling pathway that stimulates the production of pro-inflammatory cytokines. Dr. Lawrence (project 2) will investigate how association of tissue-type plasminogen activator with LRP modulates the integrity of the blood brain barrier in stroke, and the role of the integrin Mac-1 and fibrin in this response. Studies will test the hypothesis that targeting these interactions will lead to the development of more effective therapies for the treatment of ischemic stroke. Dr. Zhang (project 3) will investigated in role of tPA, LRP, PAI-1, Mac-1, and fibrin in macrophage efflux and test the hypothesis that LRP modulates this process by mediating integrin detachment and recycling. Dr. Medved (project 4) will investiage the role of fibrin(ogen) in the transendothelial migration of leukocytes, and along with Dr. Zhang will define the role of fibrin the inflammatory response. The three cores will be used by all projects to provide administratvie assistance (Core A), histology, microscopy and imaging assistance (Core B), and assistance in protein folding, proteomics and gene expression analysis (Core C).


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: 2011 ( Subtotal = $1,623,446 )
2011	2011	UNIVERSITY OF MARYLAND BALTIMORE PROFESSIONAL SCHOOLS	220 ARCH ST OFFICE LEVEL 2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Cardiovascular Diseases Research	000	15	4/4/2011	NON-COMPETING CONTINUATION	$1,623,446
														Subtotal = $1,623,446

Issue Date FY: 2010 ( Subtotal = $1,623,446 )
2010	2010	UNIVERSITY OF MARYLAND BALTIMORE PROFESSIONAL SCHOOLS	220 ARCH ST OFFICE LEVEL 2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Cardiovascular Diseases Research	000	14	3/26/2010	NON-COMPETING CONTINUATION	$1,623,446
														Subtotal = $1,623,446

Issue Date FY: 2009 ( Subtotal = $1,623,446 )
2009	2009	UNIVERSITY OF MARYLAND BALTIMORE PROFESSIONAL SCHOOLS	220 ARCH ST OFFICE LEVEL 2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Cardiovascular Diseases Research	002	13	3/23/2009	NON-COMPETING CONTINUATION	$1,623,446
2009	2008	UNIVERSITY OF MARYLAND BALTIMORE PROFESSIONAL SCHOOLS	220 ARCH ST OFFICE LEVEL 2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Cardiovascular Diseases Research	001	12	3/24/2009	NON-COMPETING CONTINUATION	$0
2009	2007	UNIVERSITY OF MARYLAND BALTIMORE PROFESSIONAL SCHOOLS	220 ARCH ST OFFICE LEVEL 2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Cardiovascular Diseases Research	000	11	3/23/2009	COMPETING CONTINUATION	$0
														Subtotal = $1,623,446

Issue Date FY: 2008 ( Subtotal = $1,623,446 )
2008	2008	UNIVERSITY OF MARYLAND BALTIMORE PROFESSIONAL SCHOOLS	220 ARCH ST OFFICE LEVEL 2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Cardiovascular Diseases Research	000	12	4/15/2008	NON-COMPETING CONTINUATION	$1,623,446
														Subtotal = $1,623,446

Issue Date FY: 2007 ( Subtotal = $1,668,704 )
2007	2007	UNIVERSITY OF MARYLAND BALTIMORE PROFESSIONAL SCHOOLS	220 ARCH ST OFFICE LEVEL 2	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Cardiovascular Diseases Research	000	11	4/10/2007	COMPETING CONTINUATION	$1,668,704
														Subtotal = $1,668,704

Issue Date FY: 2005 ( Subtotal = $1,655,469 )
2005	2005	UNIVERSITY OF MARYLAND BALTIMORE PROFESSIONAL SCHOOLS	737 WEST LOMBARD STREET	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Cardiovascular Diseases Research	000	10	5/11/2005	NON-COMPETING CONTINUATION	$1,655,469
														Subtotal = $1,655,469

Issue Date FY: 2004 ( Subtotal = $1,610,031 )
2004	2004	UNIVERSITY OF MARYLAND BALTIMORE PROFESSIONAL SCHOOLS	737 WEST LOMBARD STREET	BALTIMORE	MD	21201	BALTIMORE CITY	USA	Cardiovascular Diseases Research	000	9	7/23/2004	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$1,610,031
														Subtotal = $1,610,031

Issue Date FY: 2003 ( Subtotal = $1,483,091 )
2003	2003	AMERICAN NATIONAL RED CROSS HEADQUARTERS	600 A FOREST POINT CIRCLE	CHARLOTTE	NC	28273	MECKLENBURG	USA	Cardiovascular Diseases Research	000	8	8/7/2003	NON-COMPETING CONTINUATION	$1,483,091
														Subtotal = $1,483,091

Issue Date FY: 2002 ( Subtotal = $1,439,895 )
2002	2002	AMERICAN NATIONAL RED CROSS HEADQUARTERS	600 A FOREST POINT CIRCLE	CHARLOTTE	NC	28273	MECKLENBURG	USA	Cardiovascular Diseases Research	000	7	8/7/2002	NON-COMPETING CONTINUATION	$1,439,895
														Subtotal = $1,439,895

Issue Date FY: 2001 ( Subtotal = $1,385,979 )
2001	2001	AMERICAN NATIONAL RED CROSS HEADQUARTERS	600 A FOREST POINT CIRCLE	CHARLOTTE	NC	28273	MECKLENBURG	USA	Cardiovascular Diseases Research	000	6	9/27/2001	COMPETING CONTINUATION	$1,385,979
														Subtotal = $1,385,979

Issue Date FY: 2000 ( Subtotal = $1,555,970 )
2000	2000	AMERICAN NATIONAL RED CROSS HEADQUARTERS	600 A FOREST POINT CIRCLE	CHARLOTTE	NC	28273	MECKLENBURG	USA	Cardiovascular Diseases Research	000	5	4/12/2000	NON-COMPETING CONTINUATION	$1,555,970
														Subtotal = $1,555,970

Issue Date FY: 1999 ( Subtotal = $1,497,824 )
1999	1999	AMERICAN NATIONAL RED CROSS HEADQUARTERS	600 A FOREST POINT CIRCLE	CHARLOTTE	NC	28273	MECKLENBURG	USA	Cardiovascular Diseases Research	000	4	4/7/1999	NON-COMPETING CONTINUATION	$1,497,824
														Subtotal = $1,497,824

Issue Date FY: 1998 ( Subtotal = $1,441,713 )
1998	1998	AMERICAN NATIONAL RED CROSS HEADQUARTERS	600 A FOREST POINT CIRCLE	CHARLOTTE	NC	28273	MECKLENBURG	USA	Cardiovascular Diseases Research	001	3	5/25/1998	SUPPLEMENT FOR EXPANSION	$41,234
1998	1998	AMERICAN NATIONAL RED CROSS HEADQUARTERS	600 A FOREST POINT CIRCLE	CHARLOTTE	NC	28273	MECKLENBURG	USA	Cardiovascular Diseases Research	000	3	6/5/1998	NON-COMPETING CONTINUATION	$1,400,479
														Subtotal = $1,441,713

Grand Total All Awards = $20,232,460

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INFORMATION SIGNALING PATHWAYS IN THE VASCULATURE

Award Number: P01HL054710

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/01/1997

PERIOD OF PERFORMANCE END DATE: 03/31/2012

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