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RNA binding proteins in atherosclerosis

Award Number: R01HL139549
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2018
PERIOD OF PERFORMANCE END DATE: 01/31/2029

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RNA binding proteins in atherosclerosis - PROJECT SUMMARY Regulation of RNA biogenesis and turnover is central to the maintenance of cholesterol homeostasis and atherosclerosis development. More recently, we have come to appreciate that chemical modifications on RNA can profoundly dictate transcript fate. N6-methyladenosine methylation (m6A) is the most common RNA modification in mammalian cells. It is now established that m6A plays a critical role in cellular differentiation, organismal development, and cancer transformation. However, there is limited knowledge of the impact of RNA modifications on atherosclerosis pathways. The overarching goal of this proposal is to define the role and mechanisms of chemical modifications on RNA in atherosclerosis. Our recent studies and other abundant preliminary data, nominate m6A as a critical modulator of atherosclerosis risk factors and lesion development. In aim 1, we use genetic perturbations and vector-transduced models to investigate the importance of m6A in the control of serum cholesterol, and low-density lipoprotein uptake and test an RNA modification-based therapeutic strategy. In aim 2, we define how m6A in myeloid cells regulates cellular responses within lesions. Our assembled group of multidisciplinary scientists will work together to investigate this new layer in gene regulation. We anticipate that our proposed studies will provide important insights as to how RNA modifications impact cardiovascular health and disease and offer a provocative framework for new avenues in mitigating heart disease.


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: 2026 ( Subtotal = $674,905 )
2026	2026	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Cardiovascular Diseases Research	000	7	2/23/2026	NON-COMPETING CONTINUATION	$674,905
														Subtotal = $674,905

Issue Date FY: 2025 ( Subtotal = $710,427 )
2025	2025	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Cardiovascular Diseases Research	000	6	12/31/2024	COMPETING CONTINUATION	$710,427
														Subtotal = $710,427

Issue Date FY: 2024 ( Subtotal = -$268 )
2024	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Cardiovascular Diseases Research	000	5	8/6/2024	NON-COMPETING CONTINUATION	-$268
														Subtotal = -$268

Issue Date FY: 2022 ( Subtotal = $380,340 )
2022	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Cardiovascular Diseases Research	001	5	5/24/2022	NON-COMPETING CONTINUATION	$38,034
2022	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Cardiovascular Diseases Research	000	5	3/21/2022	NON-COMPETING CONTINUATION	$342,306
														Subtotal = $380,340

Issue Date FY: 2021 ( Subtotal = $380,529 )
2021	2021	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Cardiovascular Diseases Research	000	4	3/19/2021	NON-COMPETING CONTINUATION	$380,529
														Subtotal = $380,529

Issue Date FY: 2020 ( Subtotal = $380,715 )
2020	2020	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Cardiovascular Diseases Research	000	3	4/5/2020	NON-COMPETING CONTINUATION	$380,715
														Subtotal = $380,715

Issue Date FY: 2019 ( Subtotal = $380,897 )
2019	2019	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Cardiovascular Diseases Research	000	2	3/6/2019	NON-COMPETING CONTINUATION	$380,897
														Subtotal = $380,897

Issue Date FY: 2018 ( Subtotal = $380,491 )
2018	2018	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Cardiovascular Diseases Research	000	1	3/28/2018	NEW	$380,491
														Subtotal = $380,491

Grand Total All Awards = $3,288,036

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RNA binding proteins in atherosclerosis

Award Number: R01HL139549

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/01/2018

PERIOD OF PERFORMANCE END DATE: 01/31/2029

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