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A biochemical roadmap of exercise signal

Award Number: U24DK112340
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/14/2016
PERIOD OF PERFORMANCE END DATE: 05/31/2027

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A biochemical roadmap of exercise signal - Project Summary Exercise is an effective intervention for both the prevention and treatment of cardiometabolic diseases, but the mechanistic underpinnings of the health benefits of exercise remain incompletely defined. Recent work highlights the importance of inter-organ circuits in mediating healthful exercise responses. We identified β- aminoisobutyric acid (BAIBA) as a novel small molecule “myokine” that increases the expression of brown adipocyte-specific genes in vitro, and improves glucose disposal and decreases weight gain in mice. In humans, plasma BAIBA concentrations are increased with chronic exercise and demonstrate a strong inverse association with metabolic risk factors. Further, related efforts by our group have positioned us as leaders in characterizing within- and between-tissue molecular responses to exercise and dietary interventions. These experiences, coupled with the high translational relevance of the research problem, motivated our participation in the first phase of the MoTrPAC initiative. Our team was built upon existing collaborations between Duke, Harvard and the Broad Institute with complementary strengths in metabolomics and proteomics technologies and decades of experience in cardiometabolic research. During the initial MoTrPAC funding period, we provided a deep menu of analytical tools for targeted and non-targeted metabolomics, protein profiling, and the analysis of key protein post-translational modifications. Group members were deeply involved in the animal and pre-COVID biochemical profiling efforts, in collaborations with other Chemical Analysis Sites (CAS) and the Bioinformatics Core to harmonize work flows, and in the working groups necessary to integrate the data. We have also played key roles in associated scholarly activities and in developing the next generation of translational investigators focused on exercise science. An additional distinction of our team is the ability to integrate new findings from MoTrPAC with ongoing genomic, proteomic and metabolomic analyses in large human cohorts and other exercise studies led by our investigators. We hypothesize that integrating the metabolomic and proteomic profiles of human tissues and blood during exercise with genetics and detailed human phenotyping will provide novel insights into the inter- organ circuits and within-organ responses that mediate its salutary effects. We are deeply committed to the notion that all data generated by this multi-disciplinary consortium will be made rapidly available to the scientific community. Importantly, all four leaders of this proposed core (Carr, Clish, Gerszten and Newgard) have strong track records in the use of metabolomics and proteomics tools for the identification of novel cardiometabolic regulatory and disease mechanisms. These experiences position our CAS as one that can have maximal impact on the generation, analysis, and interpretation of molecular profiling data in the next phase of MoTrPAC.


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	2024	THE BROAD INSTITUTE, INC	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Trans-NIH Research Support	003	7	2/19/2025	COMPETING CONTINUATION	$3,702,662
2025	2022	THE BROAD INSTITUTE, INC	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Trans-NIH Research Support	001	6	2/19/2025	NON-COMPETING CONTINUATION	-$1,651,155
2025	2021	THE BROAD INSTITUTE, INC	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	5	2/19/2025	SUPPLEMENT FOR EXPANSION	-$717,832
2025	2021	THE BROAD INSTITUTE, INC	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Trans-NIH Research Support	000	5	2/19/2025	NON-COMPETING CONTINUATION	-$1,333,675
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $1 )
2024	2024	THE BROAD INSTITUTE, INC	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Trans-NIH Research Support	002	7	8/7/2024	COMPETING CONTINUATION	$1
2024	2022	THE BROAD INSTITUTE, INC	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Trans-NIH Research Support	001	6	7/30/2024	NON-COMPETING CONTINUATION	$0
2024	2022	BROAD INSTITUTE, INC., THE	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Trans-NIH Research Support	000	6	11/23/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $1

Issue Date FY: 2022 ( Subtotal = $1,651,155 )
2022	2022	BROAD INSTITUTE, INC., THE	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Trans-NIH Research Support	002	6	8/3/2022	NON-COMPETING CONTINUATION	$0
2022	2022	BROAD INSTITUTE, INC., THE	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Trans-NIH Research Support	000	6	12/6/2021	NON-COMPETING CONTINUATION	$1,651,155
2022	2021	BROAD INSTITUTE, INC., THE	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Trans-NIH Research Support	001	5	8/2/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,651,155

Issue Date FY: 2021 ( Subtotal = $3,692,086 )
2021	2021	BROAD INSTITUTE, INC., THE	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Trans-NIH Research Support	002	5	5/10/2021	NON-COMPETING CONTINUATION	$0
2021	2021	BROAD INSTITUTE, INC., THE	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Trans-NIH Research Support	000	5	12/11/2020	NON-COMPETING CONTINUATION	$2,400,207
2021	2021	BROAD INSTITUTE, INC., THE	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	003	5	9/16/2021	SUPPLEMENT FOR EXPANSION	$1,291,879
2021	2020	BROAD INSTITUTE, INC., THE	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Trans-NIH Research Support	001	4	5/10/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $3,692,086

Issue Date FY: 2020 ( Subtotal = $2,777,531 )
2020	2020	BROAD INSTITUTE, INC., THE	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Trans-NIH Research Support	002	4	7/16/2020	NON-COMPETING CONTINUATION	$0
2020	2020	BROAD INSTITUTE, INC., THE	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Trans-NIH Research Support	000	4	12/24/2019	NON-COMPETING CONTINUATION	$2,777,531
2020	2019	BROAD INSTITUTE, INC., THE	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Trans-NIH Research Support	001	3	7/16/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $2,777,531

Issue Date FY: 2019 ( Subtotal = $4,008,580 )
2019	2019	BROAD INSTITUTE, INC., THE	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Trans-NIH Research Support	003	3	7/19/2019	NON-COMPETING CONTINUATION	$0
2019	2019	BROAD INSTITUTE, INC., THE	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	3	6/17/2019	SUPPLEMENT FOR EXPANSION	$1,430,327
2019	2019	BROAD INSTITUTE, INC., THE	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Trans-NIH Research Support	000	3	12/19/2018	NON-COMPETING CONTINUATION	$2,578,253
2019	2018	BROAD INSTITUTE, INC., THE	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Trans-NIH Research Support	002	2	7/19/2019	NON-COMPETING CONTINUATION	$0
														Subtotal = $4,008,580

Issue Date FY: 2018 ( Subtotal = $1,335,796 )
2018	2018	BROAD INSTITUTE, INC., THE	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Trans-NIH Research Support	000	2	3/2/2018	NON-COMPETING CONTINUATION	$1,335,796
														Subtotal = $1,335,796

Issue Date FY: 2017 ( Subtotal = $229,143 )
2017	2017	BROAD INSTITUTE, INC., THE	415 MAIN ST	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	1	9/19/2017	SUPPLEMENT FOR EXPANSION	$116,893
2017	2017	BROAD INSTITUTE, INC., THE	7 CAMBRIDGE CTR	CAMBRIDGE	MA	02142	MIDDLESEX	USA	Trans-NIH Research Support	000	1	12/13/2016	NEW	$112,250
														Subtotal = $229,143

Grand Total All Awards = $13,694,292

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A biochemical roadmap of exercise signal

Award Number: U24DK112340

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

PERIOD OF PERFORMANCE START DATE: 12/14/2016

PERIOD OF PERFORMANCE END DATE: 05/31/2027

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