Monday, September 15, 2025 9/15/2025

Preoperative exercise therapy for surgery triggered inflammation

Award Number: R01GM137203
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/18/2020
PERIOD OF PERFORMANCE END DATE: 08/31/2022

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Preoperative exercise therapy for surgery triggered inflammation - PROJECT SUMMARY Liver ischemia and reperfusion (I/R) is an unavoidable consequence of major liver resection and liver transplantation that leads to significant morbidity, mortality, and costs after liver surgery. However, previous strategies to protect the liver from I/R injury have focused on one specific known injury mechanisms, leaving intact other detrimental processes. Pre/post-operative exercise facilitates recovery after major abdominal surgery. It is known that exercise confers beneficial effects on the surgical outcome by regulating multiple mechanisms, including alteration of quantity and function of innate immune cells to provide an anti- inflammatory environment. Our novel preliminary data indicate that preoperative exercise therapy (PET) significantly reduced serum aminotransferase levels (liver damage) and expression of cytokines and chemokines (inflammatory responses) during liver I/R. Our single-cell RNA-sequencing (scRNA-seq) data revealed PET altered the transcriptomic profile of resident Kupffer cells (KCs) towards an anti-inflammatory profile. PET also promoted the anti-inflammatory trained immunity in Kupffer cells which is associated with increased circulating damage-associated molecular pattern (DAMP) IL-33 and itaconate metabolic reprogramming. Furthermore, we show that PET significantly decreased the number of neutrophils and formation of neutrophil extracellular traps (NETs), as key mediators of local and systemic injury after liver I/R. Given these findings, we hypothesize that PET prevents liver I/R injury by altering the trained immunity in Kupffer cells, and the NET-induced local and systemic inflammatory response. We will test our hypothesis by pursuing two specific aims. In Aim 1, we will determine the mechanism by which PET protects the liver from I/R injury via training Kupffer cells towards an anti-inflammatory phenotype. We will test the hypothesis that PET induces an anti-inflammatory trained immunity in KCs via modulation of IL-33/ST2/STAT3 signaling pathway and itaconate/IRG1 metabolic reprogramming pathway. In Aim 2, we will define the role of PET in attenuating local and systemic injury during liver I/R via reduction of neutrophil extracellular traps. We will test the hypothesis that PET ameliorates systemic inflammatory injury after liver I/R through suppression of neutrophil recruitment and formation of NETs. Our proposal will delineate the molecular mechanisms of PET in the regulation of hepatic immune microenvironment, and systemic immunity during liver I/R. The mechanisms discovered in these studies will provide the foundation for not only optimizing this non-pharmacological-based strategy against surgery-induced organ injury but also devising exercise-mimicking pharmacological strategies for patients undergoing surgery who are exercise intolerant.


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 = $108,810 )
2025	2025	THE FEINSTEIN INSTITUTES FOR MEDICAL RESEARCH	350 COMMUNITY DR	MANHASSET	NY	11030	NASSAU	USA	Biomedical Research and Research Training	000	5	12/4/2024	SUPPLEMENT FOR EXPANSION	$84,018
2025	2021	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Biomedical Research and Research Training	001	2	7/31/2025	NON-COMPETING CONTINUATION	$24,792
														Subtotal = $108,810

Issue Date FY: 2024 ( Subtotal = $555,601 )
2024	2024	THE FEINSTEIN INSTITUTES FOR MEDICAL RESEARCH	350 COMMUNITY DR	MANHASSET	NY	11030	NASSAU	USA	Biomedical Research and Research Training	001	5	9/9/2024	SUPPLEMENT FOR EXPANSION	$215,000
2024	2024	THE FEINSTEIN INSTITUTES FOR MEDICAL RESEARCH	350 COMMUNITY DR	MANHASSET	NY	11030	NASSAU	USA	Biomedical Research and Research Training	000	5	8/19/2024	NON-COMPETING CONTINUATION	$340,601
														Subtotal = $555,601

Issue Date FY: 2023 ( Subtotal = $367,501 )
2023	2023	FEINSTEIN INSTITUTES FOR MEDICAL RESEARCH, THE	350 COMMUNITY DR	MANHASSET	NY	11030	NASSAU	USA	Biomedical Research and Research Training	002	4	8/7/2023	NON-COMPETING CONTINUATION	$355,967
2023	2023	FEINSTEIN INSTITUTES FOR MEDICAL RESEARCH, THE	350 COMMUNITY DR	MANHASSET	NY	11030	NASSAU	USA	Biomedical Research and Research Training	001	3	5/10/2023	SUPPLEMENT FOR EXPANSION	$11,534
2023	2022	FEINSTEIN INSTITUTES FOR MEDICAL RESEARCH, THE	350 COMMUNITY DR	MANHASSET	NY	11030	NASSAU	USA	Biomedical Research and Research Training	000	3	12/8/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $367,501

Issue Date FY: 2022 ( Subtotal = $360,125 )
2022	2022	FEINSTEIN INSTITUTES FOR MEDICAL RESEARCH, THE	350 COMMUNITY DR	MANHASSET	NY	11030	NASSAU	USA	Biomedical Research and Research Training	001	3	9/8/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$360,125
2022	2021	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Biomedical Research and Research Training	000	2	9/8/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $360,125

Issue Date FY: 2021 ( Subtotal = $335,400 )
2021	2021	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Biomedical Research and Research Training	001	2	8/6/2021	NON-COMPETING CONTINUATION	$335,400
2021	2020	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Biomedical Research and Research Training	000	1	3/19/2021	NEW	$0
														Subtotal = $335,400

Issue Date FY: 2020 ( Subtotal = $335,400 )
2020	2020	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Biomedical Research and Research Training	000	1	9/14/2020	NEW	$335,400
														Subtotal = $335,400

Grand Total All Awards = $2,062,837

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Preoperative exercise therapy for surgery triggered inflammation

Award Number: R01GM137203

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/18/2020

PERIOD OF PERFORMANCE END DATE: 08/31/2022

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