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Mechanisms associated with flares and remission in colitis

Award Number: R01DK110352
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2017
PERIOD OF PERFORMANCE END DATE: 05/31/2026

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Mechanisms associated with flares and remission in colitis - Summary Inflammatory bowel diseases (IBD) affect millions of individuals worldwide and its incidence is increasing. Both genetic and environmental factors appear to play a role in IBD development. Genetic studies in humans have linked the interleukin-23 (IL-23) signaling pathway with IBD, but the environmental factors contributing to disease, have remained elusive. The rising incidence of worldwide IBD has been associated with westernization of dietary habits in developing countries, however there is little scientific evidence to support causality. In this application we will examine the role of a particular group of dietary additives, namely food colorants, to development of colitis. We have now discovered that the food colorant Red 40, also known as Allura Red AC, promotes colitis in mice that conditionally express low levels of IL-23 (referred to as R23FR mice), but not in wild type mice. Red 40 is the most abundant food colorant in the world, with annual production exceeding 2.3 million kg. It is widely used in as red colorant in soft drinks, cherry flavored products, candy, dairy, drugs, and cosmetics. Of interest, the Red 40-containing beverages, Kool-Aid and the hydrating solution Pedialyte Cherry can also cause colitis in R23FR mice. Red 40-induced colitis in R23FR mice requires the microbiota and CD4+ T cells. Based on these and other results presented here, we formulate a central hypothesis that the Red 40 or its metabolites haptenize bacterial or endogenous proteins to generate tolerance in wild type mice, or colitis in mice in which IL-23 expression is dysregulated. We will study in this proposal the mechanisms involved in generation and prevention of these responses. Specifically, we will define: 1) if Red 40 and its metabolite ANSA are haptens; 2) how Red 40 induces tolerance in control mice; and 3) if Red 40 or ANSA-specific T cells are generated in R23FR mice


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: 2027 ( Subtotal = $0 )
2027	2025	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	9	10/26/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $734,202 )
2025	2025	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	9	5/29/2025	NON-COMPETING CONTINUATION	$734,202
														Subtotal = $734,202

Issue Date FY: 2024 ( Subtotal = $704,833 )
2024	2024	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	8	6/4/2024	NON-COMPETING CONTINUATION	$704,833
														Subtotal = $704,833

Issue Date FY: 2023 ( Subtotal = $734,202 )
2023	2023	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	7	5/23/2023	NON-COMPETING CONTINUATION	$734,202
														Subtotal = $734,202

Issue Date FY: 2022 ( Subtotal = $701,092 )
2022	2022	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	6	5/17/2022	NON-COMPETING CONTINUATION	$701,092
2022	2021	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	5	10/28/2021	COMPETING CONTINUATION	$2,860
2022	2020	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	10/28/2021	NON-COMPETING CONTINUATION	-$2,860
														Subtotal = $701,092

Issue Date FY: 2021 ( Subtotal = $719,393 )
2021	2021	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	6/25/2021	COMPETING CONTINUATION	$719,393
														Subtotal = $719,393

Issue Date FY: 2020 ( Subtotal = $381,375 )
2020	2020	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	3/24/2020	NON-COMPETING CONTINUATION	$381,375
														Subtotal = $381,375

Issue Date FY: 2019 ( Subtotal = $381,375 )
2019	2019	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	4/26/2019	NON-COMPETING CONTINUATION	$381,375
														Subtotal = $381,375

Issue Date FY: 2018 ( Subtotal = $381,375 )
2018	2018	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	4/25/2018	NON-COMPETING CONTINUATION	$381,375
														Subtotal = $381,375

Issue Date FY: 2017 ( Subtotal = $381,375 )
2017	2017	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	ONE GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	4/20/2017	NEW	$381,375
														Subtotal = $381,375

Grand Total All Awards = $5,119,222

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Mechanisms associated with flares and remission in colitis

Award Number: R01DK110352

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/01/2017

PERIOD OF PERFORMANCE END DATE: 05/31/2026

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