# Sex-Specific Differences in the Development of Anthracycline Cardiotoxicity

> **NIH NIH R21** · BETH ISRAEL DEACONESS MEDICAL CENTER · 2020 · $218,750

## Abstract

PROJECT SUMMARY
This proposal seeks to define the mechanisms that contribute to sex-specific differences in anthracycline
cardiotoxicity. The project will be led by Dr. Aarti Asnani, a physician-investigator at Beth Israel Deaconess
Medical Center (BIDMC) and an Instructor at Harvard Medical School (HMS). Based on her chemistry
background and clinical expertise, Dr. Asnani is uniquely well-positioned to characterize the biochemical
pathways that contribute to anthracycline cardiotoxicity in order to identify new cardioprotective strategies.
Dr. Asnani was recruited to BIDMC in 2017, where she currently serves as the Associate Director of the
Cardio-Oncology Program. For this project, she will collaborate with Dr. Robert Gerszten, Chief of
Cardiovascular Medicine at BIDMC and Professor of Medicine at Harvard Medical School. Dr. Gerszten has
extensive experience in mass spectrometry-based metabolomic profiling to uncover new mechanisms of
cardiometabolic disease. He will serve as an advisor for Dr. Asnani’s project and supervise the mass
spectrometry experiments outlined in her proposal. For statistical analyses of data collected from the BIDMC
retrospective cardiotoxicity patient registry, Dr. Asnani will work specifically with Michelle Keyes, PhD, a senior
statistician in Dr. Gerszten’s group. Dr. Keyes received her PhD under the mentorship of Dr. Martin Laron, who
is Director of Statistics for the Framingham Heart Study and Professor of Medicine at Boston University
Medical Center. Dr. Pier Paolo Pandolfi will also serve as a collaborator and advisor for Dr. Asnani’s project,
given his extensive experience in cancer biology and the use of mouse models to develop antitumor therapies.
He is the Director of the BIDMC Cancer Center and Cancer Research Institute, Chief of the Division of
Genetics in the BIDMC Department of Medicine, and a Professor of Medicine and Pathology at Harvard
Medical School. At BIDMC, Dr. Asnani benefits from strong institutional support and a rich research
environment. She has access to a broad range of core facilities and equipment, scientific expertise, and
opportunities for collaboration that extend across BIDMC, the Longwood Medical Area, and HMS.
In this proposal, Dr. Asnani has outlined a series of approaches to elucidate the role of estrogen metabolism as
a potential mediator of sexual dimorphism in anthracycline cardiotoxicity. Using a mouse model of chronic
doxorubicin cardiomyopathy, she will determine how modulation of CYP1-mediated estradiol metabolism
confers cardioprotection in a sex-specific manner. She will also investigate how sex-specific differences in
mitochondrial biogenesis contribute to the development of cardiotoxicity in this model. Finally, she will assess
the role of estrogen metabolism in the BIDMC retrospective cardiotoxicity registry, which includes 1954
patients treated with anthracyclines for non-estrogen-dependent tumors. If successful, this line of investigation
may enable the use of higher...

## Key facts

- **NIH application ID:** 9978912
- **Project number:** 5R21HL148748-02
- **Recipient organization:** BETH ISRAEL DEACONESS MEDICAL CENTER
- **Principal Investigator:** Aarti Asnani
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $218,750
- **Award type:** 5
- **Project period:** 2019-08-01 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9978912

## Citation

> US National Institutes of Health, RePORTER application 9978912, Sex-Specific Differences in the Development of Anthracycline Cardiotoxicity (5R21HL148748-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9978912. Licensed CC0.

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