# Microtubule Regulated Mechanotransduction in Skeletal Muscle

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 2021 · $466,851

## Abstract

Abstract
Mechano-activation of both reactive oxygen species (ROS) and calcium (Ca2+) signaling has
been widely reported in diverse cell types, including skeletal muscle. We are now investigating
the mechanisms by which mechano-activated ROS and Ca2+ influence the physiology of normal
muscle, as well as the pathophysiology following their dysregulation in muscular dystrophy. This
proposal builds upon our recent provocative discovery and characterization of "X-ROS
signaling" which suggested that many critical elements of mechano-signaling arise from the
microtubules, their mechano-activation of NADPH oxidase type 2 (NoX2) ROS production (i.e.,
X-ROS), and its subsequent activation of sarcolemmal Ca2+ channels. We demonstrated that
acutely targeting X-ROS components provided a therapeutic benefit in pre-clinical models of
muscular dystrophy. Based on our previous research, we have devised a set of specific aims,
using both control and genetically altered mice, which will extend our previous discoveries and
further characterize the physiologic relevance of X-ROS signaling. The proposed single cell
studies are enabled by state-of-the-art techniques, including many newly devised within the
laboratory, that allow simultaneous measurements of force, intracellular [Ca2+], Ca2+ influx, and
[ROS]i while controlling sarcomere length. These, combined with advanced biochemistry and
immunofluorescence, allow the advancement of relevant findings to in vitro whole muscle and in
vivo animal studies designed to inform future pre-clinical efficacy studies.

## Key facts

- **NIH application ID:** 10242047
- **Project number:** 5R01AR071618-05
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Christopher William WARD
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $466,851
- **Award type:** 5
- **Project period:** 2017-09-21 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10242047

## Citation

> US National Institutes of Health, RePORTER application 10242047, Microtubule Regulated Mechanotransduction in Skeletal Muscle (5R01AR071618-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10242047. Licensed CC0.

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