# Cardiac ubiquitin ligases: regulation and role in modulating cardiac excitation.

> **NIH NIH R01** · RHODE ISLAND HOSPITAL · 2020 · $584,548

## Abstract

Abstract
A prolonged QT interval increases the likelihood for ventricular arrhythmias and sudden
cardiac death. Although 16 genes have been identified in causing long QT syndrome,
these mutations are rare and can therefore account for a small percentage of patients
with malignant ventricular arrhythmias. Recent genome-wide association studies
identified five loci associated with a prolonged QT interval. These polymorphisms may
directly and cumulatively contribute to QT interval prolongation and therefore to cardiac
arrhythmias. One of the aforementioned loci maps upstream of the gene coding for
LITAF, which plays an important role in protein turnover. The overall goal of this study is
to investigate the role of LITAF in QT interval regulation. This project will employ in vivo
and in vitro experimental approaches including the use of zebrafish, cardiac specific
knock out of LITAF in mice, and neonatal and adult rabbit cardiomyocytes. We
hypothesize that LITAF acts as a regulator for cardiac NEDD4 ubiquitin ligases
modulating cardiac excitation. Aim 1 will explore the mechanisms through which LITAF
regulates L-type calcium channels and sodium channels in vivo (zebrafish and mice),
whereas Aim 2 will study the mechanisms underlying the LITAF-dependent regulation of
voltage-gated sodium and calcium channels in vitro, and LITAF regulation of specific
NEDD4 ligases that modulate these channels.

## Key facts

- **NIH application ID:** 9974406
- **Project number:** 5R01HL134706-04
- **Recipient organization:** RHODE ISLAND HOSPITAL
- **Principal Investigator:** GIDEON KOREN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $584,548
- **Award type:** 5
- **Project period:** 2017-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9974406

## Citation

> US National Institutes of Health, RePORTER application 9974406, Cardiac ubiquitin ligases: regulation and role in modulating cardiac excitation. (5R01HL134706-04). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9974406. Licensed CC0.

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