# Thioredoxin, a novel agent for mitigating radiation-induced hematopoietic injury

> **NIH NIH R56** · DUKE UNIVERSITY · 2022 · $443,371

## Abstract

Project Summary
Radiation exposure and radiation injury remain a real and constant threat not only to our armed service men and
women, but also to our public health. Hematopoietic stem cells (HSCs) and hematopoiesis are among the most
sensitive tissues/organs to radiation injury and hematopoietic syndrome remains the first therapeutic challenge
following radiation injury. Currently, there are very few - if any - agents that can be used to rescue lethal dose
radiation injury and enhance all-lineage hematopoietic cell recovery when given 24 hours after irradiation.
Continued existence of this gap represents an important problem to our care for patients exposed to radiation.
The preliminary study by the applicant demonstrated marked protective and proliferative effects of thioredoxin
on HSCs and a significant survival advantage of giving thioredoxin 24 hours after irradiation. The long-term goal
is to develop thioredoxin into a “deliverable” agent for the treatment of radiation-related hematopoietic injury. The
overall objective in this application are to determine the molecular mechanisms through which thioredoxin
regulates HSC function and protects HSCs from radiation injury. Additionally, as a prelude to clinical application
the thioredoxin administration regimen will be optimized and the protective effects of thioredoxin will be
determined in non-human primates. The central hypothesis is that thioredoxin mitigates against radiation injury
by improving the survival and expansion of long-term repopulating HSCs. These hypotheses have been
formulated on the basis of preliminary data produced in the applicant’s laboratory. The rationale for the proposed
research is that, once it is known how thioredoxin protects HSCs from radiation injury and the effectiveness of
thioredoxin is optimized and tested in both mice and non-human primates, we will be able to move forward into
clinical use, generating a new and innovative approach for the treatment of patients with radiation related injury.
Guided by strong preliminary data, this hypothesis will be tested by pursuing two specific aims: Aim 1 is to define
the molecular mechanisms through which thioredoxin regulates HSC function and protects HSCs from radiation
injury. The role of p53 signaling pathway in thioredoxin mediated radiation protection will be investigated. The
role of thioredoxin in embryonic hematopoiesis will be determined using intravital imaging technique with single
cell resolution. Aim 2 is to optimize thioredoxin administration regimen in mice and determine the protective
effects of thioredoxin in humanized mice and in non-human primates. Additionally, the combinatorial effects of
thioredoxin and hematopoietic cell growth factors (G-CSF) in mitigating against radiation injury will be
determined. The approach is innovative, in the applicant’s opinion, because it focuses on a novel protein that is
effective in mitigating the toxic effects of radiation when given after 24 hours of radiation e...

## Key facts

- **NIH application ID:** 10687418
- **Project number:** 1R56HL155582-01A1
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Yubin Kang
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $443,371
- **Award type:** 1
- **Project period:** 2022-09-09 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10687418

## Citation

> US National Institutes of Health, RePORTER application 10687418, Thioredoxin, a novel agent for mitigating radiation-induced hematopoietic injury (1R56HL155582-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10687418. Licensed CC0.

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