# Recombinant Fc Chimeras of R-spondin 1 and Slit2 for Medical Countermeasure of Chronic Radiation Syndrome

> **NIH NIH UH3** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $26,001

## Abstract

Few medical countermeasures are currently available to treat chronic multi-organ failures following exposure to
life-threatening radiation during radiation emergencies and nuclear disasters, especially for aged victims.
Endogenous adult stem cells (ASCs), also called tissue-specific stem cells, exist, often in a scarce quantity, in
almost every adult tissues and organs. However, how to robustly induce ASCs by administering soluble
molecules to repair the injured organs, which could be more clinically applicable and cost-effective, remains
largely unknown. We found that systemic administration of recombinant Fc chimeras of human R-spondin 1
and Slit2 (rRspo1-Fc/rSlit2-Fc) protected young mice from death, even when given 24 hours after lethal doses
of whole body irradiation (WBI). Mechanistically, WBI induced the expression of Robo1 in intestinal stem cells
(ISCs) and hematopoietic stem cells (HSCs). Rspo1 acted synergistically with Slit2 to enhance the survival of
irradiated ISCs and HSCs and to accelerate the repair of radiation-induced acute gut and bone marrow injuries.
In this proposal, we will test (1) the efficacy of rRspo1-Fc/rSlit2-Fc in mitigation of chronic radiation syndrome
in young and older male and female mice, and (2) the long-term effects of rRspo1-Fc/rSlit2-Fc in irradiated
young and older male and female mice. We believe that the regimen of rRspo1-Fc/rSlit2-Fc may provide a safe
and effective pharmacological method to stimulate the repair of radiation-mediated chronic damage of essential
tissues in aged victims.

## Key facts

- **NIH application ID:** 10221298
- **Project number:** 3UH3AI128900-04S1
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** JIAN-GUO GENG
- **Activity code:** UH3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $26,001
- **Award type:** 3
- **Project period:** 2016-09-27 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10221298

## Citation

> US National Institutes of Health, RePORTER application 10221298, Recombinant Fc Chimeras of R-spondin 1 and Slit2 for Medical Countermeasure of Chronic Radiation Syndrome (3UH3AI128900-04S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10221298. Licensed CC0.

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