Tuesday, July 1, 2025 7/1/2025

Immune Cell Interactions in Atherosclerosis

Award Number: P01HL136275
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2017
PERIOD OF PERFORMANCE END DATE: 05/31/2027

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Immune Cell Interactions in Atherosclerosis - Overall Abstract Our PPG will test the hypothesis that the lipid and protein components of lipoproteins trigger innate and adaptive immune responses that control human atherosclerosis. We will study the immune cell cross-talk that occurs during human atherosclerosis progression. Immunity plays an important role in coronary artery disease (CAD), as recent clinical trials have clearly demonstrated. However, these trials also taught us that systemic treatments of the immune system, by their very nature, impair host defense. Thus, it is imperative to find new, more specific interventions that modulate immune cell function in atherosclerosis, yet spare host defense. We will study immune cells and plasma from human subjects from 3 well-characterized clinical cohorts, 1-our existing CAVA cohort (Coronary Assessment at Virginia), where subjects are enrolled from the UVA cardiac catheterization laboratory that undergo quantitative coronary analysis for disease quantification; 2- Computerized Tomography (CT)-CAVA cohort, where subjects undergoing noninvasive CT angiography for cardiovascular disease assessment in years 1 and 2 of the PPG renewal (baseline measures) will be followed up at 3 years to allow for determination of coronary plaque progression and changes in markers of plaque vulnerability, and 3- The Multi-Ethnic Study of Atherosclerosis (MESA), a large NHLBI-sponsored longitudinal cohort that has been ongoing since 2000. In this synergistic program, Project 1 CD9+ Monocyte and Macrophage Immune Functions in Atherosclerosis has identified new monocyte subsets expressing the tetraspanin CD9, and will study how CD9 impacts metabolism and immune modulation of monocytes and macrophages in CAD. Project 2 Cholesterol Regulation of Inflammatory Macrophages in Atherosclerosis will study how specialized lipid raft signaling drives transcriptional and metabolic reprogramming in macrophages. Project 3 Regulation of Atheroprotective IgM-producing B cells in Murine and Human Atherosclerosis will study how CD24 and CCR6 on newly identified human B-1 cell subsets modulate atheroprotective IgM production. Project 4 ApoB-Specific CD4 and CD8 T cells Exacerbate Atherosclerosis will identify and study immunodominant human apolipoprotein B (apoB) epitopes to investigate how these activate CD4 and CD8 T cell using mouse models to address mechanisms. An important synergistic aspect to our PPG is that it is highly interactive, in that B cells, T cells, monocytes and macrophages communicate with each other in the artery wall and in lymphoid tissues. Unique aspects of our program are the focus on studying human immune cells, the link to biospecimens and clinical data from 3 complementary cardiovascular cohorts, the use of unbiased high dimensional protein and RNA-sequencing at the single cell level for all human immune cells from the same human subjects, and our ability to link all of our group’s discoveries with extensive clinical data on each subject. The human studies are complemented by murine mechanistic models where applicable. The end goal of our studies is to identify safe new therapeutic strategies targeting immune cell function to limit CAD.


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 = $2,358,435 )
2025	2025	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC	AUGUSTA UNIVERSITY 1120 15TH STREET	AUGUSTA	GA	30912	RICHMOND	USA	Cardiovascular Diseases Research	000	10	5/30/2025	NON-COMPETING CONTINUATION	$2,358,435
														Subtotal = $2,358,435

Issue Date FY: 2024 ( Subtotal = $2,306,703 )
2024	2024	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC	AUGUSTA UNIVERSITY 1120 15TH STREET	AUGUSTA	GA	30912	RICHMOND	USA	Cardiovascular Diseases Research	005	9	5/30/2024	NON-COMPETING CONTINUATION	$2,311,266
2024	2022	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC	AUGUSTA UNIVERSITY 1120 15TH STREET	AUGUSTA	GA	30912	RICHMOND	USA	Cardiovascular Diseases Research	003	7	12/12/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$841,687
2024	2022	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Cardiovascular Diseases Research	002	6	12/12/2023	COMPETING CONTINUATION	-$841,687
2024	2022	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Cardiovascular Diseases Research	001	6	12/11/2023	COMPETING CONTINUATION	$551,946
2024	2021	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Cardiovascular Diseases Research	000	5	12/11/2023	NON-COMPETING CONTINUATION	-$551,946
2024	2020	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Cardiovascular Diseases Research	004	4	12/13/2023	SUPPLEMENT FOR EXPANSION	-$4,563
														Subtotal = $2,306,703

Issue Date FY: 2023 ( Subtotal = $2,358,435 )
2023	2023	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC.	1120 15TH ST STE CJ3301	AUGUSTA	GA	30912	RICHMOND	USA	Cardiovascular Diseases Research	001	8	6/8/2023	NON-COMPETING CONTINUATION	$2,358,435
2023	2022	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC.	1120 15TH ST STE CJ3301	AUGUSTA	GA	30912	RICHMOND	USA	Cardiovascular Diseases Research	000	7	4/17/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $2,358,435

Issue Date FY: 2022 ( Subtotal = $2,648,176 )
2022	2022	AUGUSTA UNIVERSITY RESEARCH INSTITUTE, INC.	1120 15TH ST STE CJ3301	AUGUSTA	GA	30912	RICHMOND	USA	Cardiovascular Diseases Research	003	7	7/14/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$2,358,435
2022	2022	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Cardiovascular Diseases Research	002	6	7/13/2022	COMPETING CONTINUATION	-$2,358,435
2022	2022	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Cardiovascular Diseases Research	001	6	12/22/2021	COMPETING CONTINUATION	$2,648,176
2022	2020	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Cardiovascular Diseases Research	000	4	12/7/2021	SUPPLEMENT FOR EXPANSION	$0
2022	2020	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Cardiovascular Diseases Research	004	4	7/28/2022	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $2,648,176

Issue Date FY: 2021 ( Subtotal = $2,577,670 )
2021	2021	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Cardiovascular Diseases Research	000	5	6/18/2021	NON-COMPETING CONTINUATION	$2,577,670
														Subtotal = $2,577,670

Issue Date FY: 2020 ( Subtotal = $3,101,584 )
2020	2020	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Cardiovascular Diseases Research	001	4	8/14/2020	SUPPLEMENT FOR EXPANSION	$523,914
2020	2020	LA JOLLA INSTITUTE FOR IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Cardiovascular Diseases Research	000	4	6/10/2020	NON-COMPETING CONTINUATION	$2,577,670
														Subtotal = $3,101,584

Issue Date FY: 2019 ( Subtotal = $2,577,670 )
2019	2019	LA JOLLA INSTITUTE FOR ALLERGY AND IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Cardiovascular Diseases Research	000	3	5/31/2019	NON-COMPETING CONTINUATION	$2,577,670
														Subtotal = $2,577,670

Issue Date FY: 2018 ( Subtotal = $2,577,497 )
2018	2018	LA JOLLA INSTITUTE FOR ALLERGY AND IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Cardiovascular Diseases Research	000	2	6/8/2018	NON-COMPETING CONTINUATION	$2,577,497
														Subtotal = $2,577,497

Issue Date FY: 2017 ( Subtotal = $2,675,593 )
2017	2017	LA JOLLA INSTITUTE FOR ALLERGY AND IMMUNOLOGY	9420 ATHENA CIR	LA JOLLA	CA	92037	SAN DIEGO	USA	Cardiovascular Diseases Research	000	1	6/22/2017	NEW	$2,675,593
														Subtotal = $2,675,593

Grand Total All Awards = $23,181,763

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Immune Cell Interactions in Atherosclerosis

Award Number: P01HL136275

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/01/2017

PERIOD OF PERFORMANCE END DATE: 05/31/2027

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