# Mechanisms of Purkinje Cell Remodeling

> **NIH NIH R01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2024 · $847,164

## Abstract

PROJECT SUMMARY
The ventricular conduction system (VCS) is essential for normal myocardial excitation and contraction.
Diseases impacting VCS structure and function are responsible for a substantial burden of cardiovascular
disease, including conduction slowing and block, and triggered and reentrant arrhythmias. In previous NIH-
funded work, our laboratory established and characterized novel genetic tools to visualize the formation and
function of the murine VCS and its constituent Purkinje cells, resulting in the identification of a novel
transcriptional pathway critical for VCS development. We also used these tools to create and characterize
innovative genetically engineered murine models that firmly established the role of Purkinje cells or juxta-
Purkine cells as arrhythmogenic triggers in heritable syndromes including CPVT and LQT3. While our earlier
studies significantly advanced the field's understanding of the role of Purkinje cells in mono- and oligogenic
forms of arrhythmogenic heart disease, much less is known about the underlying mechanistic basis for
pathologic remodeling of the VCS in common acquired cardiomyopathies, such as those that seen in patients
with hypertension, diabetes, obesity and other common conditions. These disease states are by far
responsible for the greatest burden of cardiovascular morbidity and mortality. We have obtained preliminary
data suggesting that paracrine signaling from activated fibroblasts may drive Purkinje cell transcriptional
remodeling, as evidenced by repression of the rapid conduction signature and induction of a pro-fibrotic
program. Based upon these data, we propose two specific aims designed to provide a deep mechanistic
understanding of pathologic remodeling of Purkinje cells. We also will perform exploratory studies to determine
if agents that target fibroblast activation can diminish pathologic Purkinje cell remodeling.

## Key facts

- **NIH application ID:** 10977853
- **Project number:** 1R01HL171118-01A1
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Glenn I Fishman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $847,164
- **Award type:** 1
- **Project period:** 2024-07-01 → 2028-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10977853

## Citation

> US National Institutes of Health, RePORTER application 10977853, Mechanisms of Purkinje Cell Remodeling (1R01HL171118-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10977853. Licensed CC0.

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