# Directing Tryptophan Immunometabolism to Ameliorate Liver Ischemic-Reperfusion Injury

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2024 · $616,580

## Abstract

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.

## Key facts

- **NIH application ID:** 10769860
- **Project number:** 5R01DK129690-03
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Benjamin George Keselowsky
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $616,580
- **Award type:** 5
- **Project period:** 2022-04-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10769860

## Citation

> US National Institutes of Health, RePORTER application 10769860, Directing Tryptophan Immunometabolism to Ameliorate Liver Ischemic-Reperfusion Injury (5R01DK129690-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10769860. Licensed CC0.

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