# Immunomodulation of Galectin-3 to Prevent Radiation-Induced Myocardial Fibrogenesis

> **NIH NIH R01** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2021 · $279,125

## Abstract

Immunomodulation of Galectin-3 to Prevent Radiation-Induced Myocardial Fibrogenesis
 This application addresses the scientific goals of FOA-PA-19-112. More than half of life-threatening
thoracic cancers are treated with repeated doses of ionizing radiation. Unfortunately, the pro-inflammatory and
pro-fibrotic properties of ionizing radiation increase the cumulative risk of cardiac damage. Galectin-3 (gal3) is a
unique carbohydrate and peptide-binding molecule widely implicated in myocardial inflammation and fibrosis.
Increased myocardial gal3 expression is reported in models of cardiac irradiation, but it is unclear whether gal3
directly contributes to radiation-induced cardiac fibrosis. We aim to determine the function of gal3 in mediating
the inflammatory and fibrotic effects of radiation. We propose to test the hypothesis that gal3 mediates
radiation-induced myocardial inflammation and fibrosis, and that genetic or immunological modulation
of gal3 expression or function neutralizes these effects and is thus cardioprotective. The unique features
of this hypothesis are the concept that radiation exposure activates cardiomyocytes and macrophages to release
gal3, which then binds to high-affinity mast cell surface receptors inducing the release of inflammatory and fibrotic
mediators. Moreover, we have designed a new gal3 immunomodulatory vaccine that neutralizes gal3 after
single-dose intramuscular administration in a mouse model. To test the general hypothesis, we propose three
specific aims.
 In Aim I, we will determine the effects of gal3 modulation on inflammation, fibrosis, and cardiac function
after repeated exposure to thoracic radiation. We will use genetically engineered cardiomyocyte-selective gal3
gain-of-function mice to study gal3-myocyte-fibroblast pathways, and bone marrow transplanted mice to study
gal3-macrophage-fibroblast pathways. In Aim II, we will determine the contribution of gal3 released by
cardiomyocytes and macrophages to activate mast cells after in vitro irradiation, as well as the downstream
effects on cardiac fibroblast growth and collagen synthesis using a state-of-the art microchamber system. In Aim
III, we will compare the preventive and therapeutic effects of a new gal3-immunomodulatory vaccine on radiation-
induced cardiac fibrogenesis and dysfunction. The feasibility of this project is confirmed by the a) availability of
gal3 knockout mice for gal3 loss-of-function studies, b) cardio-selective and global gal3 overexpression mice
for cardiac and systemic gain-of-function studies, and c) Myeloablated mice engrafted with gal3-null or gal3-
overexpressing progenitor cells for macrophage-targeted gal3 loss-and gain-of-function studies. A safe and
highly potent gal3 inhibitor vaccine has been designed in our laboratory to study the therapeutic potential of gal3
inhibition. Expected project outcomes include the evidence that gal3 mediates cardiac fibrosis and dysfunction
after cumulative radiation exposure, and pre-cl...

## Key facts

- **NIH application ID:** 10120082
- **Project number:** 1R01HL152090-01A1
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** Umesh C Sharma
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $279,125
- **Award type:** 1
- **Project period:** 2021-03-01 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10120082

## Citation

> US National Institutes of Health, RePORTER application 10120082, Immunomodulation of Galectin-3 to Prevent Radiation-Induced Myocardial Fibrogenesis (1R01HL152090-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10120082. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*