# Identifying novel networks of candidate Atrial Fibrillation genes in the Drosophila cardiac aging model

> **NIH NIH F32** · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · 2021 · $68,562

## Abstract

Project Summary/Abstract
 Atrial fibrillation (AF), the most common heart rhythm disorder, is reaching epidemic proportions in the aging
population, affecting nearly 33 million people worldwide. The incidence of AF increases with age, with individuals
over the age of 65 having a 9% chance of developing this arrhythmia. AF is the leading cause of heart failure
and stroke in human populations, and as the average lifespan continues to increase, so will the rates of these
disorders. However, the molecular etiology of AF is not well defined and treatment options are limited.
Additionally, there is evidence that common substrates link AF with other arrhythmia types and heart disease
(e.g. long QT syndrome). Recent research has identified both common genetic variants that increase AF
susceptibility in the general population and rare genetic variants linked to AF, suggesting that AF is likely a
multifactorial disease whose etiology involves network(s) of interacting genetic variants. Resolving these
complex interactions modulating cardiac function in AF is impractical in mammalian systems, but approachable
using Drosophila genetics. Drosophila provide an advantage in unraveling the largely unknown genetic regulators of
heart dysfunction due to the reduced genetic redundancy and high degree of conservation in the underlying pathways
and cellular mechanisms. A subset of AF-associated candidate genes likely interact in a combinatorial manner with
age and diet to cause cardiac arrhythmicity. Preliminary screens of candidate AF-related genes in both the fly
heart and in human induced pluripotent stem cell atrial-like cardiomyocytes (hiPSC-ACMs) have identified a
network of genes that suggests interactions between stearoyl-CoA desaturase (SCD) and two AF-associated
genes, KCNA5 and phospholamban (PLN). SCD, a key lipid metabolic enzyme, is known to disrupt sarcoplasmic
reticulum calcium ATPase pump (SERCA) activity, however, a KCNA5-SCD-SERCA-PLN network has not been
well demonstrated in cardiac tissue. Cardiac phenotyping of interactions found in AF networks in both model
systems will identify novel and likely conserved genetic pathways, providing novel therapeutic strategies. Sanford
Burnham Prebys (SBP) is an environment that is highly supportive of research and collaborative interdisciplinary
approaches, with extensive shared resources providing investigators with both cutting-edge equipment and
technical expertise. Dr. Kezos has already mastered a number of complementary scientific concepts and
approaches that he is using to address his research questions. Additionally, the Ocorr Laboratory is staffed with
talented postdoctoral fellows and staff scientists who will be of assistance to Dr. Kezos during the research
training. With the proposed training in the hiPSC model system, bioinformatics pipelines and CRISPR-Cas9
gene editing, Dr. Kezos will be well equipped to launch an impactful and independent research career to
investigate the genetics of cardiomy...

## Key facts

- **NIH application ID:** 10155141
- **Project number:** 1F32HL156607-01
- **Recipient organization:** SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE
- **Principal Investigator:** James Kezos
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $68,562
- **Award type:** 1
- **Project period:** 2021-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10155141

## Citation

> US National Institutes of Health, RePORTER application 10155141, Identifying novel networks of candidate Atrial Fibrillation genes in the Drosophila cardiac aging model (1F32HL156607-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10155141. Licensed CC0.

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