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Directing Tryptophan Immunometabolism to Ameliorate Liver Ischemic-Reperfusion Injury

Award Number: R01DK129690
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: 04/01/2022
PERIOD OF PERFORMANCE END DATE: 12/31/2025

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Directing Tryptophan Immunometabolism to Ameliorate Liver Ischemic-Reperfusion Injury - Project Summary/Abstract Many different disease states and surgical interventions result in a period of inadequate tissue/organ blood supply (i.e., ischemia), that result in reperfusion injury when blood flow is restored, known as ischemia-reperfusion injury (IRI). IRI causes local inflammation, cell death, excessive tissue destruction and possible organ failure. Examples are found in transplantation, trauma, myocardial infarction, stroke, and in particular, IRI is a main cause of liver dysfunction and failure after liver surgery. Unfortunately, there are currently no therapies available in clinical practice addressing IRI, where a major problem is the harmful systemic side effects and toxicities of existing drugs. To address this problem, we are innovating a new therapeutic technology aiming to program immune cells toward a metabolic state blocking excessive inflammation by directing tryptophan metabolism through delivery of an enzyme into circulation. This represents a new class of anti- inflammatory/immunosuppressive biologic drug, with potential to limit systemic toxicities/side effects, and with potential to be significantly less immunocompromising. Lack of treatment options for liver IRI and a catalog of in vivo preliminary data strongly supporting the foundational rationale of IDO as an innovative new anti-inflammatory agent, make this proposal highly significant. Looking to the future, success would open opportunity to expand to other anti-inflammatory applications, for example, pre-conditioning donor grafts for transplantation.


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 = $569,158 )
2025	2025	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	12/23/2024	NON-COMPETING CONTINUATION	$569,158
														Subtotal = $569,158

Issue Date FY: 2024 ( Subtotal = $691,549 )
2024	2024	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	12/20/2023	NON-COMPETING CONTINUATION	$578,045
2024	2024	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	3	5/30/2024	NON-COMPETING CONTINUATION	$38,535
2024	2024	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	3	1/4/2024	SUPPLEMENT FOR EXPANSION	$74,969
														Subtotal = $691,549

Issue Date FY: 2023 ( Subtotal = $769,811 )
2023	2023	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	1/26/2023	NON-COMPETING CONTINUATION	$654,230
2023	2023	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	2/8/2023	SUPPLEMENT FOR EXPANSION	$115,581
														Subtotal = $769,811

Issue Date FY: 2022 ( Subtotal = $713,884 )
2022	2022	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	1	9/1/2022	SUPPLEMENT FOR EXPANSION	$37,510
2022	2022	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	3/21/2022	NEW	$676,374
														Subtotal = $713,884

Grand Total All Awards = $2,744,402

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Directing Tryptophan Immunometabolism to Ameliorate Liver Ischemic-Reperfusion Injury

Award Number: R01DK129690

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: 04/01/2022

PERIOD OF PERFORMANCE END DATE: 12/31/2025

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