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Role of Eosinophils in Hepatic Ischemia Reperfusion Injury

Award Number: R01DK121330
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: 06/01/2019
PERIOD OF PERFORMANCE END DATE: 03/31/2027

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Role of Eosinophils in Hepatic Ischemia Reperfusion Injury - PROJECT SUMMARY The goal of this proposal is to investigate the functional role of eosinophils in promoting tissue repair and regeneration after hepatic ischemia and reperfusion (IR) injury. Hepatic IR injury, which occurs during transplantation surgery, is a major factor contributing to acute liver dysfunction and long-term complications. Timely and robust liver repair and regeneration is vital to the resolution and recovery from ischemic liver damage. Thus, there is a critical need to identify key pro-reparative molecular and cellular mechanisms in order to develop therapeutic strategies to improve the outcomes of liver surgery and transplantation. Our preliminary data demonstrated that the peak of eosinophil accumulation in the liver after IR injury coincided with the critical time point of liver repair and regeneration. Eosinophil-deficient mice exhibited markedly delayed and impaired tissue repair after hepatic IR injury. In contrast, adoptive transfer of WT bone marrow-derived eosinophils (bmEos) to eosinophil-deficient mice dramatically improved liver repair to a similar rate and extent as in the WT mice. However, interleukin (IL)-4- and IL-13-deficient bmEos could not improve liver repair. We also found reduced EGFR activation and lower levels of HB-EGF in eosinophil-deficient mice. Together, these findings support our hypothesis that eosinophil-derived IL-4 and/or IL-13, through inducing HB-EGF production, play an essential role in promoting tissue repair after hepatic IR injury. We propose three Specific Aims to (1) Investigate the role of eosinophils in liver repair after IR injury, (2) Elucidate the mechanism by which eosinophils promote liver repair after IR injury, and (3) Explore the potential of targeting eosinophils to accelerate liver repair after IR injury.


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: 2026 ( Subtotal = $446,267 )
2026	2026	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	7000 FANNIN ST FL 9	HOUSTON	TX	77030	HARRIS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	8	3/4/2026	NON-COMPETING CONTINUATION	$446,267
														Subtotal = $446,267

Issue Date FY: 2025 ( Subtotal = $446,267 )
2025	2025	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	7000 FANNIN ST FL 9	HOUSTON	TX	77030	HARRIS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	7	4/29/2025	NON-COMPETING CONTINUATION	$446,267
														Subtotal = $446,267

Issue Date FY: 2024 ( Subtotal = $424,965 )
2024	2024	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	7000 FANNIN ST FL 9	HOUSTON	TX	77030	HARRIS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	6	5/9/2024	NON-COMPETING CONTINUATION	$424,965
2024	2023	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	7000 FANNIN ST FL 9	HOUSTON	TX	77030	HARRIS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	5	3/4/2024	COMPETING CONTINUATION	$202,724
2024	2022	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON	7000 FANNIN ST FL 9	HOUSTON	TX	77030	HARRIS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	3/4/2024	NON-COMPETING CONTINUATION	-$202,724
														Subtotal = $424,965

Issue Date FY: 2023 ( Subtotal = $455,625 )
2023	2023	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON, THE	7000 FANNIN ST	HOUSTON	TX	77030	HARRIS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	5	4/21/2023	COMPETING CONTINUATION	$455,625
2023	2022	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON, THE	7000 FANNIN ST	HOUSTON	TX	77030	HARRIS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	4/13/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $455,625

Issue Date FY: 2022 ( Subtotal = $388,331 )
2022	2022	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON, THE	7000 FANNIN ST	HOUSTON	TX	77030	HARRIS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	3/30/2022	NON-COMPETING CONTINUATION	$388,331
														Subtotal = $388,331

Issue Date FY: 2021 ( Subtotal = $388,331 )
2021	2021	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON, THE	7000 FANNIN ST	HOUSTON	TX	77030	HARRIS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	3/5/2021	NON-COMPETING CONTINUATION	$388,331
														Subtotal = $388,331

Issue Date FY: 2020 ( Subtotal = $386,585 )
2020	2020	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON, THE	7000 FANNIN ST	HOUSTON	TX	77030	HARRIS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	3/12/2020	NON-COMPETING CONTINUATION	$386,585
														Subtotal = $386,585

Issue Date FY: 2019 ( Subtotal = $397,641 )
2019	2019	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT HOUSTON, THE	7000 FANNIN ST	HOUSTON	TX	77030	HARRIS	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	5/28/2019	NEW	$397,641
														Subtotal = $397,641

Grand Total All Awards = $3,334,012

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Role of Eosinophils in Hepatic Ischemia Reperfusion Injury

Award Number: R01DK121330

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: 06/01/2019

PERIOD OF PERFORMANCE END DATE: 03/31/2027

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