# The Effects of Estrogen on Cardiac Arrhythmic Propensity

> **NIH NIH K99** · STANFORD UNIVERSITY · 2020 · $128,787

## Abstract

PROJECT SUMMARY
This proposal describes a five-year career development program to prepare Dr. Ilanit Itzhaki for a career as an
independent investigator. This program will build on Dr. Itzhaki's background as a stem cell biologist and
experimental electrophysiologist by enhancing her knowledge base in sex hormones in cardiovascular health
and disease and providing her expertise in molecular cardiology and medicinal chemistry for translational
research in drug discovery and sex-specific therapeutics. Dr. Itzhaki will be mentored by Dr. Joseph Wu,
Director of the Stanford Cardiovascular Institute. The proposed mentor is an expert in stem cell biology,
pharmacogenomics, and drug discovery utilizing iPSC-derived cardiomyocytes (iPSC-CMs). To complement
Dr. Wu's mentorship, Dr. Itzhaki will be co-mentored by Dr. Marcia Stefanick, Director of the Stanford Women
& Sex Differences in Medicine Center, and an expert in the field of sex hormones and cardiovascular health
and disease. The K99 phase of Dr. Itzhaki's training will consist of structured mentorship by the primary mentor
and co-mentor, complementary meetings with the advisory committee, formal coursework, a provocative
research project, and a program for career transition. For symptomatic long QT syndrome (LQTS) patients
prone to life threatening cardiac arrhythmia, pregnancy can facilitate a unique period of anti-arrhythmic
protection, when estrogen hormone level is at its highest. Deciphering the anti-arrhythmic contribution of
estrogen can lead to the identification of much-needed new anti-arrhythmic therapeutic targets and the design
of novel therapeutic entities. In the K99 phase of this proposal, Dr. Itzhaki will assess the effect of estrogen on
arrhythmic propensity using female and male LQT patient-specific iPSC-CMs at the single cell and multicellular
levels (Aim 1). Dr. Itzhaki will then identify mechanistic intracellular targets that facilitate estrogen's anti-
arrhythmic benefit (Aim 2). The identified beneficial antiarrhythmic targets, will help guide Dr. Itzhaki in the R00
phase, in the design of an estrogen analogue, which will be assessed for sustained anti-arrhythmic benefits
and absence of cardiotoxicity (Aim 3), with the intention of proposing new therapeutic entities that take
advantage of hormone-based anti-arrhythmic benefits, yet at the same time allow the treatment of both male
and female patients at all ages. Collectively, the insights acquired from Dr. Itzhaki's proposal can contribute
significantly to the treatment of LQTS patients, specifically, and arrhythmia-susceptible congenital disease
patients, in general, and promote the growing field of sex-specific therapeutics. Furthermore, using iPSC-CMs
as a "dish-to-bedside" approach, to aid in the design of anti-arrhythmic therapeutic analogues and to serve as
a high-throughput analogue-screening platform, will greatly contribute to the prospect of translational medicine.
Finally, this work will provide a foundation for f...

## Key facts

- **NIH application ID:** 9981489
- **Project number:** 5K99HL143211-02
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Ilanit Itzhaki
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $128,787
- **Award type:** 5
- **Project period:** 2019-08-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9981489

## Citation

> US National Institutes of Health, RePORTER application 9981489, The Effects of Estrogen on Cardiac Arrhythmic Propensity (5K99HL143211-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9981489. Licensed CC0.

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