# Mechanisms of Lamin A/C-mediated Cardiac Conduction Disorders

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2024 · $704,071

## Abstract

PROJECT SUMMARY
The cardiac conduction system (CCS) is specialized in the generation and propagation of electrical impulses
from the atria to the ventricles to produce a highly coordinated muscle contraction. Cardiac conduction disorders
(CCDs) including sick sinus syndrome, atrioventricular block (AVB), and bundle branch block are common
arrhythmic disorders that impact the contraction of atria or ventricles. Cardiac pacing is the standard treatment
for patients with symptomatic bradyarrhythmia resulting in implantation of over 600,000 pacemakers annually in
US due to sinus node dysfunction (SND) or AVB. Currently, there is no alternative treatment for these patients.
Thus, understanding the molecular and cellular mechanisms leading to CCD may provide a foundation for new
therapeutic strategies. A nonsense mutation (c.C673>T, p.R225>X) in lamin A/C (LMNA) identified in a kindred,
was associated progressive CCD and atrial arrhythmias, preceding the development of cardiomyopathy and
heart failure. The mechanistic link between mutated lamin A/C and CCD is largely undetermined. Preliminary
results suggest that the LMNA-R255X knockin mice develop CCD phenotype, similar to patient carriers of R225X
mutation. The proposed work will elucidate the molecular mechanisms by which mutation in lamin A/C promote
CCD. Our study will establish the pathological function of lamin A/C in CCD development. The molecular
pathways uncovered from this study will likely have a broader impact on our understanding of the molecular
mechanisms of CCD in the general population.

## Key facts

- **NIH application ID:** 10802802
- **Project number:** 1R01HL166832-01A1
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Mihail Gabriel Chelu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $704,071
- **Award type:** 1
- **Project period:** 2024-09-25 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10802802

## Citation

> US National Institutes of Health, RePORTER application 10802802, Mechanisms of Lamin A/C-mediated Cardiac Conduction Disorders (1R01HL166832-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10802802. Licensed CC0.

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