# Smad8 is a driver of Duchenne muscular dystrophy pathology via myomiR repression

> **NIH NIH K08** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2021 · $193,056

## Abstract

Project Summary: This project proposes to study the role of Smad8 and muscle-enriched microRNAs, known
as myomiRs, in Duchenne muscular dystrophy. Duchenne muscular dystrophy is a skeletal muscle wasting
disease that is at least in part mediated by secondary effects from membrane fragility due to loss of dystrophin.
These secondary effects include impairments in muscle proliferation, differentiation, and regeneration that are
propagated by inflammation. This project has identified the TGF-associated transcription factor, Smad8, as
markedly elevated and associated with the repression of myomiRs in Duchenne muscular dystrophy skeletal
muscles. As such, the proposal will use cell culture and mouse models of Duchenne muscular dystrophy to
molecularly map the role of Smad8 in skeletal muscle function and disease.
The short-term goal is to identify the mechanisms by which TGF / Smad8 signaling might promote dystrophic
processes by understanding its connection to myomiRs repression with a goal of identifying novel pathways for
potential therapeutic intervention. For example, we will study the effects of over-expression and knockdown of
Smad8 on key pathways like muscle proliferation, differentiation, and skeletal muscle regeneration. We will also
study impact of Smad8 modulation on myomiRs and their downstream mRNA pathways. The long-term goal is
to expand our understanding of TGF / Smad8 cell signaling and microRNA biology in skeletal muscle function
in health and disease.

## Key facts

- **NIH application ID:** 10104343
- **Project number:** 1K08NS120812-01
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Michael Alonzo Lopez
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $193,056
- **Award type:** 1
- **Project period:** 2020-12-01 → 2025-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10104343

## Citation

> US National Institutes of Health, RePORTER application 10104343, Smad8 is a driver of Duchenne muscular dystrophy pathology via myomiR repression (1K08NS120812-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10104343. Licensed CC0.

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