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The role of epigenetic transcriptional memory in monocyte-macrophage cells and cardiovascular disease risk

Award Number: K01HL140271
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 07/15/2018
PERIOD OF PERFORMANCE END DATE: 06/30/2023

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The role of epigenetic transcriptional memory in monocyte-macrophage cells and cardiovascular disease risk - Project Summary/Abstract This proposal details a five-year training program to support the candidate to achieve his long-term career goal of building a successful independent transdisciplinary research program featuring clinical, immunology, and epigenetic research to address the impact of epigenetic transcriptional memory in immune cells on cardiovascular disease (CVD) risk in minority populations. The candidate has a strong scientific skillset and knowledge in epigenetics that provides a solid background to ensure his success in pursuing transdisciplinary clinical research focused on CVD. The candidate seeks to focus his career development and enhance his experience and technical research skills in immunology and clinical CVD research. The candidate will acquire essential research skills including flow cytometry, in vitro and ex-vivo monocyte/macrophage functional assays of human cells, and integrative bioinformatics to establish his independence in using his expertise in epigenetics to address CVD. He has already established his own independent research project aimed at defining the role of epigenetic regulation of monocyte/macrophage cellular responses across ethnicities with CVD health disparities. The scientific and institutional environment at the University of Hawaii is well-matched to ensuring the candidate achieves his career goals to study the immune system and CVD. There are multiple independently funded research programs such as the Center for Cardiovascular Disease Research, COBRE Diabetes Center, and Research Multidisciplinary and Translational Research Infrastructure Expansion project that will provide shared resources and core facilities and offer numerous collaborative opportunities in cardiometabolic disease research. A key component of the research career development plan is mentorship from a multi-disciplinary mentoring team focused on cardiovascular disease research consisting of immunology, clinical, and health disparity research experts committed toward contributing their expertise to support the candidate’s career development and expand his research training. The candidate will pursue a hypothesis that dysfunctional monocyte responses associated with high cardiovascular disease risk are related to epigenomic programming differences at inflammatory and metabolic genes and are exacerbated in Native Hawaiians compared to Caucasians. To test this hypothesis, a cross-sectional study of viably cryopreserved blood specimens from 200 Native Hawaiians and age gender research project aimed at addressing the matched Caucasians with clinically defined high and low CVD risk. The specific aims are (1) To measure and compare functional responses of isolated monocyte and macrophage cells from NHOPI and Caucasians with clinically defined low or high CVD risk in the Multiethnic cohort. (2) Determine if epigenetically regulated inflammatory and metabolic genes in isolated monocyte cells from NHOPI and Caucasians associate with CVD risk and differ by ethnicity. (3) Within monocytes from high CVD risk NHOPI and Caucasians, to examine the impact of metformin on the epigenetic state of inflammatory and metabolic genes.


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: 2024 ( Subtotal = -$5,049 )
2024	2022	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	575 LEXINGTON AVE FL 9	NEW YORK	NY	10022	NEW YORK	USA	Cardiovascular Diseases Research	000	5	1/22/2024	NON-COMPETING CONTINUATION	-$5,049
														Subtotal = -$5,049

Issue Date FY: 2022 ( Subtotal = $157,641 )
2022	2022	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	1300 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Cardiovascular Diseases Research	001	5	6/28/2022	NON-COMPETING CONTINUATION	$157,641
2022	2021	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	1300 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Cardiovascular Diseases Research	000	4	1/29/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $157,641

Issue Date FY: 2021 ( Subtotal = $157,641 )
2021	2021	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	1300 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Cardiovascular Diseases Research	002	4	7/3/2021	NON-COMPETING CONTINUATION	$157,641
2021	2020	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	1300 YORK AVE	NEW YORK	NY	10065	NEW YORK	USA	Cardiovascular Diseases Research	001	3	5/25/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$84,312
2021	2019	UNIVERSITY OF HAWAII SYSTEMS	2425 CAMPUS RD SINCLAIR RM 1	HONOLULU	HI	96822	HONOLULU	USA	Cardiovascular Diseases Research	000	2	5/25/2021	NON-COMPETING CONTINUATION	-$84,312
														Subtotal = $157,641

Issue Date FY: 2020 ( Subtotal = $157,641 )
2020	2020	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	407 E 61ST ST RM 106 1ST FL	NEW YORK	NY	10065	NEW YORK	USA	Cardiovascular Diseases Research	001	3	8/7/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$157,641
2020	2019	UNIVERSITY OF HAWAII SYSTEMS	2425 CAMPUS RD SINCLAIR RM 1	HONOLULU	HI	96822	HONOLULU	USA	Cardiovascular Diseases Research	000	2	8/6/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $157,641

Issue Date FY: 2019 ( Subtotal = $157,641 )
2019	2019	UNIVERSITY OF HAWAII SYSTEMS	2425 CAMPUS RD SINCLAIR RM 1	HONOLULU	HI	96822	HONOLULU	USA	Cardiovascular Diseases Research	000	2	6/27/2019	NON-COMPETING CONTINUATION	$157,641
														Subtotal = $157,641

Issue Date FY: 2018 ( Subtotal = $157,641 )
2018	2018	UNIVERSITY OF HAWAII SYSTEMS	2425 CAMPUS RD SINCLAIR RM 1	HONOLULU	HI	96822	HONOLULU	USA	Cardiovascular Diseases Research	000	1	7/13/2018	NEW	$157,641
2018	2018	UNIVERSITY OF HAWAII SYSTEMS	2425 CAMPUS RD SINCLAIR RM 1	HONOLULU	HI	96822	HONOLULU	USA	Cardiovascular Diseases Research	001	1	8/24/2018	NEW	$0
														Subtotal = $157,641

Grand Total All Awards = $783,156

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The role of epigenetic transcriptional memory in monocyte-macrophage cells and cardiovascular disease risk

Award Number: K01HL140271

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 07/15/2018

PERIOD OF PERFORMANCE END DATE: 06/30/2023

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