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Lung endothelial cell phenotypes

Award Number: P01HL066299
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/01/2001
PERIOD OF PERFORMANCE END DATE: 10/31/2024

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Lung endothelial cell phenotypes - PROJECT SUMMARY Endothelium lines blood vessels and interconnects all organ systems. However, endothelial cells exhibit a rich diversity in structure and function. Such heterogeneity is apparent between endothelial cells in different organs, in endothelial cells along a single vascular segment within an organ, and between immediately adjacent cells. This program project grant is founded on the overall hypothesis that endothelium lining pulmonary arteries, capillaries, and veins is phenotypically distinct, where each cell type is specialized to fulfill the unique demands of its vascular niche. Specialization among these cells is encoded by discrete organization of second messenger signaling networks. Therefore, in this competitive renewal each of our projects examines the organization and function of endothelial cell signaling networks. We evaluate the origin of second messenger signals, how these signals spread inside of the cell, what limits the lifespan of the signals, and which effector proteins are principally activated by the signals. For the first time we can measure three-dimensional spread of second messengers in realistic cellular geometries over time. Bacteria such as Pseudomonas aeruginosa impair endothelial cell function during the course of infection that culminates in acute lung injury. P. aeruginosa alters the organization and function of second messenger signaling, and in some instances, the bacterium utilizes enzymes that generate second messenger signals during the host- pathogen interaction. P. aeruginosa and its exoenzymes disrupt the endothelial cell barrier, and hence, our projects use this bacterium and its toxins to probe determinants of endothelial heterogeneity and function, including barrier integrity. All projects take advantage of vertically integrated approaches, ranging from the use of cultured cells (e.g. with control for substrate stiffness) to various in situ (e.g. isolated organs, lung slices, isolated blood vessels, and cell-free lung scaffolds) and in vivo preparations. In each of these cases, attention is paid to what is similar, and what is dissimilar, about the respective cell phenotypes. Altogether, projects systematically address three specific aims or objectives, to: (1) identify and test novel molecular mechanisms (e.g. signatures) that are responsible for site-specific endothelial cell function, especially in the microcirculation, (2) determine the importance of these mechanisms in preclinical models of disease, and (3) translate novel therapeutic approaches to preclinical models of disease. Projects are highly interactive. Defining mechanisms that underlie second messenger signaling networks will not only inform us as to the nature of endothelial cell heterogeneity, but provide unprecedented insight into host-pathogen interactions that disrupt the endothelial cell barrier and cause tissue edema. Mechanistic insight into endothelial signal transduction networks will reveal novel therapeutic approaches to improve endothelial dysfunction.


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	2022	UNIVERSITY OF SOUTH ALABAMA	307 N UNIVERSITY BLVD	MOBILE	AL	36608	MOBILE	USA	Lung Diseases Research	000	20	4/24/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2022	UNIVERSITY OF SOUTH ALABAMA	307 N UNIVERSITY BLVD	MOBILE	AL	36608	MOBILE	USA	Lung Diseases Research	000	20	8/3/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $1,987,388 )
2022	2022	UNIVERSITY OF SOUTH ALABAMA	307 UNIVERISTY BLVD 380 ADMINISTRATION BLDG	MOBILE	AL	36688	MOBILE	USA	Lung Diseases Research	000	20	8/16/2022	NON-COMPETING CONTINUATION	$1,987,388
														Subtotal = $1,987,388

Issue Date FY: 2021 ( Subtotal = $2,030,508 )
2021	2021	UNIVERSITY OF SOUTH ALABAMA	307 UNIVERISTY BLVD 380 ADMINISTRATION BLDG	MOBILE	AL	36688	MOBILE	USA	Lung Diseases Research	000	19	5/7/2021	NON-COMPETING CONTINUATION	$2,030,508
														Subtotal = $2,030,508

Issue Date FY: 2020 ( Subtotal = $2,048,988 )
2020	2020	UNIVERSITY OF SOUTH ALABAMA	307 UNIVERISTY BLVD 380 ADMINISTRATION BLDG	MOBILE	AL	36688	MOBILE	USA	Lung Diseases Research	003	18	6/18/2020	NON-COMPETING CONTINUATION	$2,039,748
2020	2020	UNIVERSITY OF SOUTH ALABAMA	307 UNIVERISTY BLVD 380 ADMINISTRATION BLDG	MOBILE	AL	36688	MOBILE	USA	Lung Diseases Research	001	17	3/30/2020	SUPPLEMENT FOR EXPANSION	$0
2020	2020	UNIVERSITY OF SOUTH ALABAMA	307 UNIVERISTY BLVD 380 ADMINISTRATION BLDG	MOBILE	AL	36688	MOBILE	USA	Lung Diseases Research	000	17	3/13/2020	SUPPLEMENT FOR EXPANSION	$10,590
2020	2020	UNIVERSITY OF SOUTH ALABAMA	307 UNIVERISTY BLVD 380 ADMINISTRATION BLDG	MOBILE	AL	36688	MOBILE	USA	Lung Diseases Research	002	17	6/10/2020	SUPPLEMENT FOR EXPANSION	-$1,350
														Subtotal = $2,048,988

Issue Date FY: 2019 ( Subtotal = $1,987,388 )
2019	2019	UNIVERSITY OF SOUTH ALABAMA	307 UNIVERISTY BLVD 380 ADMINISTRATION BLDG	MOBILE	AL	36688	MOBILE	USA	Lung Diseases Research	000	17	6/22/2019	NON-COMPETING CONTINUATION	$1,987,388
														Subtotal = $1,987,388

Issue Date FY: 2018 ( Subtotal = $1,982,011 )
2018	2018	UNIVERSITY OF SOUTH ALABAMA	380 ADMINISTRATION BUILDING	MOBILE	AL	36688	MOBILE	USA	Lung Diseases Research	000	16	5/10/2018	COMPETING CONTINUATION	$1,982,011
2018	2016	UNIVERSITY OF SOUTH ALABAMA	307 UNIVERISTY BLVD 380 ADMINISTRATION BLDG	MOBILE	AL	36688	MOBILE	USA	Lung Diseases Research	001	15	7/18/2018	EXTENSION WITH OR WITHOUT FUNDS	$0
														Subtotal = $1,982,011

Issue Date FY: 2016 ( Subtotal = $1,838,357 )
2016	2016	UNIVERSITY OF SOUTH ALABAMA	307 UNIVERSITY BOULEVARD	MOBILE	AL	36688	MOBILE	USA	Lung Diseases Research	000	15	5/27/2016	EXTENSION WITH OR WITHOUT FUNDS	$1,838,357
														Subtotal = $1,838,357

Issue Date FY: 2015 ( Subtotal = $1,810,783 )
2015	2015	UNIVERSITY OF SOUTH ALABAMA	307 UNIVERSITY BOULEVARD	MOBILE	AL	36688	MOBILE	USA	Lung Diseases Research	000	14	4/3/2015	NON-COMPETING CONTINUATION	$1,810,783
														Subtotal = $1,810,783

Issue Date FY: 2014 ( Subtotal = $1,801,589 )
2014	2014	UNIVERSITY OF SOUTH ALABAMA	307 UNIVERSITY BOULEVARD	MOBILE	AL	36688	MOBILE	USA	Lung Diseases Research	000	13	4/7/2014	NON-COMPETING CONTINUATION	$1,801,589
														Subtotal = $1,801,589

Issue Date FY: 2013 ( Subtotal = $1,750,114 )
2013	2013	UNIVERSITY OF SOUTH ALABAMA	307 UNIVERSITY BOULEVARD	MOBILE	AL	36688	MOBILE	USA	Lung Diseases Research	000	12	4/18/2013	NON-COMPETING CONTINUATION	$1,654,522
2013	2013	UNIVERSITY OF SOUTH ALABAMA	307 UNIVERSITY BOULEVARD	MOBILE	AL	36688	MOBILE	USA	Lung Diseases Research	001	12	7/9/2013	NON-COMPETING CONTINUATION	$95,592
														Subtotal = $1,750,114

Issue Date FY: 2012 ( Subtotal = $1,838,357 )
2012	2012	UNIVERSITY OF SOUTH ALABAMA	307 UNIVERSITY BOULEVARD	MOBILE	AL	36688	MOBILE	USA	Lung Diseases Research	000	11	5/14/2012	COMPETING CONTINUATION	$1,838,357
2012	2010	UNIVERSITY OF SOUTH ALABAMA	307 UNIVERSITY BOULEVARD	MOBILE	AL	36688	MOBILE	USA	Lung Diseases Research	001	10	5/14/2012	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,838,357

Issue Date FY: 2010 ( Subtotal = $1,862,279 )
2010	2010	UNIVERSITY OF SOUTH ALABAMA	307 UNIVERSITY BOULEVARD	MOBILE	AL	36688	MOBILE	USA	Lung Diseases Research	000	10	7/16/2010	NON-COMPETING CONTINUATION	$1,862,279
														Subtotal = $1,862,279

Issue Date FY: 2009 ( Subtotal = $1,826,361 )
2009	2009	UNIVERSITY OF SOUTH ALABAMA	307 UNIVERSITY BOULEVARD	MOBILE	AL	36688	MOBILE	USA	Lung Diseases Research	001	9	7/17/2009	NON-COMPETING CONTINUATION	$1,543,601
2009	2009	UNIVERSITY OF SOUTH ALABAMA	307 UNIVERSITY BOULEVARD	MOBILE	AL	36688	MOBILE	USA	Trans-NIH Recovery Act Research Support	000	8	6/5/2009	SUPPLEMENT FOR EXPANSION	$16,202
2009	2009	UNIVERSITY OF SOUTH ALABAMA	307 UNIVERSITY BOULEVARD	MOBILE	AL	36688	MOBILE	USA	Lung Diseases Research	002	9	8/3/2009	SUPPLEMENT FOR EXPANSION	$266,558
														Subtotal = $1,826,361

Issue Date FY: 2008 ( Subtotal = $1,726,165 )
2008	2008	UNIVERSITY OF SOUTH ALABAMA	307 UNIVERSITY BOULEVARD	MOBILE	AL	36688	MOBILE	USA	Lung Diseases Research	000	8	7/9/2008	NON-COMPETING CONTINUATION	$1,726,165
														Subtotal = $1,726,165

Issue Date FY: 2007 ( Subtotal = $1,707,603 )
2007	2007	UNIVERSITY OF SOUTH ALABAMA	307 UNIVERSITY BOULEVARD	MOBILE	AL	36688	MOBILE	USA	Lung Diseases Research	000	7	6/27/2007	NON-COMPETING CONTINUATION	$1,707,603
														Subtotal = $1,707,603

Issue Date FY: 2006 ( Subtotal = $1,720,527 )
2006	2006	UNIVERSITY OF SOUTH ALABAMA	307 UNIVERSITY BOULEVARD	MOBILE	AL	36688	MOBILE	USA	Lung Diseases Research	000	6	8/9/2006	COMPETING CONTINUATION	$1,720,527
														Subtotal = $1,720,527

Issue Date FY: 2005 ( Subtotal = $1,386,809 )
2005	2005	UNIVERSITY OF SOUTH ALABAMA	307 UNIVERSITY BOULEVARD	MOBILE	AL	36688	MOBILE	USA	Lung Diseases Research	000	5	7/21/2005	NON-COMPETING CONTINUATION	$1,386,809
														Subtotal = $1,386,809

Issue Date FY: 2004 ( Subtotal = $1,348,985 )
2004	2004	UNIVERSITY OF SOUTH ALABAMA	307 UNIVERSITY BOULEVARD	MOBILE	AL	36688	MOBILE	USA	Lung Diseases Research	000	4	7/26/2004	NON-COMPETING CONTINUATION	$1,348,985
														Subtotal = $1,348,985

Issue Date FY: 2003 ( Subtotal = $1,322,769 )
2003	2003	UNIVERSITY OF SOUTH ALABAMA	307 UNIVERSITY BOULEVARD	MOBILE	AL	36688	MOBILE	USA	Lung Diseases Research	000	3	7/29/2003	NON-COMPETING CONTINUATION	$1,322,769
														Subtotal = $1,322,769

Issue Date FY: 2002 ( Subtotal = $1,287,531 )
2002	2002	UNIVERSITY OF SOUTH ALABAMA	307 UNIVERSITY BOULEVARD	MOBILE	AL	36688	MOBILE	USA	Lung Diseases Research	000	2	7/30/2002	NON-COMPETING CONTINUATION	$1,287,531
														Subtotal = $1,287,531

Grand Total All Awards = $34,581,052

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Lung endothelial cell phenotypes

Award Number: P01HL066299

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 12/01/2001

PERIOD OF PERFORMANCE END DATE: 10/31/2024

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