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The Study of Families with Heritable Crohn's Disease to Support Rational Design of Microbiodata-Based Therapies

Award Number: K23DK119544
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 02/24/2021
PERIOD OF PERFORMANCE END DATE: 12/31/2024

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The Study of Families with Heritable Crohn's Disease to Support Rational Design of Microbiodata-Based Therapies - Project Summary/Abstract The cause of Crohn's disease (CD) is believed to be rooted in the interactions between genetic susceptibilities and exposures to environmental factors, such as specific gut microbes. Unfortunately, the complexity of these interactions makes it difficult to understand what portion of CD risk is modifiable, and particularly whether gut microbiome compositions can be altered to overcome one's underlying and fixed genetic predisposition. This proposal will address whether individuals at high genetic risk for CD, but who never develop disease, harbor characteristic gut microbial signatures that signal protection from CD. It will furthermore address whether protective microbiomes can be transferred to diminish, delay, or prevent CD activity in others. Aim 1 will entail the study of multigenerational families with multiplex CD – with the rationale that families, sharing common living environments, meals, and behaviors, will minimize common confounders of human microbiome studies. Individuals will be stratified by a polygenic risk score to better identify those at highest genetic risk but remain disease-free and who are hypothesized as being most likely to harbor intestinal microbiomic and metabolomic signatures that characterize disease protection. In Aim 2, select fecal biospecimens (collected in Aim 1) containing putative protective microbiomes will be transplanted into a germ-free CD mouse model. These mice will then be characterized by their phenotypic, microbial, metabolomic, and immune responses and assessed for alterations in disease onset and severity. These studies will provide insights into microbially-mediated modulators of CD activity; for example, clarifying the yet unknown reason why fecal transplants are very effective for only a small portion of inflammatory bowel disease cases and why outcomes appear to be heavily donor-dependent. Coupling the study of an enriched human population with an animal model, to mechanistically test candidate protective microbiomes, will streamline the scientific approach and expedite the transition of promising study findings into clinical care. The scientific proposal and associated training plan will furthermore prepare the PI, so that she will be well-equipped to lead future studies of host-microbe dynamics in inflammatory bowel disease as an independent translational investigator.


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 = $217,323 )
2024	2024	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	65 BERGEN ST	NEWARK	NJ	07107	ESSEX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	5	12/22/2023	NON-COMPETING CONTINUATION	$217,323
2024	2023	RUTGERS THE STATE UNIVERSITY OF NEW JERSEY	65 BERGEN ST	NEWARK	NJ	07107	ESSEX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	10/16/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$171,904
2024	2022	RUTGERS, THE STATE UNIVERSITY	675 HOES LN	PISCATAWAY	NJ	08854	MIDDLESEX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	3	10/16/2023	NON-COMPETING CONTINUATION	-$171,904
														Subtotal = $217,323

Issue Date FY: 2023 ( Subtotal = $218,150 )
2023	2023	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	65 BERGEN ST	NEWARK	NJ	07107	ESSEX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	1/12/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$218,150
2023	2022	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	675 HOES LN	PISCATAWAY	NJ	08854	MIDDLESEX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	3	1/12/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $218,150

Issue Date FY: 2022 ( Subtotal = $218,953 )
2022	2022	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	675 HOES LN	PISCATAWAY	NJ	08854	MIDDLESEX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	12/23/2021	NON-COMPETING CONTINUATION	$218,953
														Subtotal = $218,953

Issue Date FY: 2021 ( Subtotal = $219,899 )
2021	2021	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	675 HOES LN	PISCATAWAY	NJ	08854	MIDDLESEX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	4/2/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$219,899
2021	2021	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	675 HOES LN	PISCATAWAY	NJ	08854	MIDDLESEX	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	003	2	7/31/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$111,050
2021	2020	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	1	7/31/2021	NEW	-$111,050
2021	2020	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	4/2/2021	NEW	$0
														Subtotal = $219,899

Issue Date FY: 2020 ( Subtotal = $197,412 )
2020	2020	NEW YORK UNIVERSITY	550 1ST AVE	NEW YORK	NY	10016	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	1/16/2020	NEW	$197,412
														Subtotal = $197,412

Grand Total All Awards = $1,071,737

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The Study of Families with Heritable Crohn's Disease to Support Rational Design of Microbiodata-Based Therapies

Award Number: K23DK119544

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 02/24/2021

PERIOD OF PERFORMANCE END DATE: 12/31/2024

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