# Mechanisms for cell signaling in the control of cardiomyogenesis

> **NIH NIH R01** · UNIVERSITY OF SOUTH FLORIDA · 2022 · $940,216

## Abstract

Project Summary/Abstract
Down syndrome (DS), the condition caused by trisomy of human chromosome 21, affects approximately 1 in
700 newborns in the United States. Congenital heart defects (CHDs) are very frequent in children with DS with
a prevalence of 50% compared to a risk of < 1% in typical children. Although remarkable advances in health
care and cardiac correction surgery have improved the survival rate of children born with DS, CHDs are still a
primary and significant risk factor for mortality in people with DS through age twenty. Using a combination of the
human induced pluripotent stem cell (iPSC)-based model and Dp(16)1Yey/+ (Dp16), a mouse model for DS, we
identified increased dosage of interferon (IFN) receptor encoded by genes, IFNAR1, IFNAR2, IFNG2, and
IL 10RB on chromosome 21 (chr21) as a causative factor of CHDs in DS. The canonical Wnt signaling pathway
was down-regulated during DS cardiogenesis in vitro and in vivo. Normalization of IFN signaling restored the
canonical Wnt pathway and ameliorated cardiogenesis in DS. In this project, we propose to (1) determine
molecular mechanisms by which increased IFN signaling down-regulates the Wnt/β-Catenin pathway during
heart development in DS and (2) examine cell populations associated with response to increased IFN signaling
during heart development in DS. The results from this project have the potential to facilitate the development of
novel therapeutic strategies to benefiting both people with DS and typical children born with CHDs.

## Key facts

- **NIH application ID:** 10914374
- **Project number:** 7R01HL133230-07
- **Recipient organization:** UNIVERSITY OF SOUTH FLORIDA
- **Principal Investigator:** Kunhua Song
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $940,216
- **Award type:** 7
- **Project period:** 2024-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10914374

## Citation

> US National Institutes of Health, RePORTER application 10914374, Mechanisms for cell signaling in the control of cardiomyogenesis (7R01HL133230-07). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10914374. Licensed CC0.

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