# Identifying critical mediators of ovarian and cardiovascular health

> **NIH NIH K99** · BROWN UNIVERSITY · 2024 · $118,661

## Abstract

PROJECT SUMMARY/ABSTRACT
 Environmental contaminant exposure accounts for 20-30% of the known congenital heart disease and is
a significant driver of adult heart disease. Likewise, exposure to environmental contamination also adversely
affects ovarian health and is thought to be a significant factor in the global rise of infertility rates. Cardiac health
is impacted by ovarian health and vice versa. While the heart supplies the ovary with necessary oxygen, the
ovary produces estrogen, which is cardioprotective. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure is
associated with both cardiac and ovarian dysfunction. However, the effects of TCDD exposure on organ health
are often studied in isolation and, therefore, the interaction between the two systems is lost. This proposal
investigates the central hypothesis that juvenile TCDD exposure affects female heart health by compromising
ovarian function. There is a critical need to understand the mediators of TCDD toxicity in both the heart and
ovary to provide effective treatment for heart disease and infertility. In Aim 1, I will determine the ovarian
contribution to TCDD-induced cardiovascular toxicity. In Aim 2, I will use single-cell sequencing to identify unique
and shared cellular and molecular targets of TCDD in the heart and ovary. In Aim 3, I will determine whether
TCDD-induced infertility results from disrupted functioning of the blood-follicle barrier.
 My long-term goal is to become an independent investigator at an R1 institution studying reproductive
toxicology. My lab will use zebrafish to model human reproductive development and exposure to environmental
chemicals. I have designed a training plan that will expand my scientific skill set as well as guide my professional
development. My mentor, Dr. Jessica Plavicki, and co-mentor, Dr. Jodi Flaws, will facilitate my growth and
provide research and career support. I have assembled an advisory team that is made up of experts who will
provide critical research and career guidance. By achieving the specific milestones outlined in my training plan
and research strategy, I will develop a strong foundation for my future research program and academic career.

## Key facts

- **NIH application ID:** 10866060
- **Project number:** 1K99ES036311-01
- **Recipient organization:** BROWN UNIVERSITY
- **Principal Investigator:** Michelle E Kossack
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $118,661
- **Award type:** 1
- **Project period:** 2024-04-10 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10866060

## Citation

> US National Institutes of Health, RePORTER application 10866060, Identifying critical mediators of ovarian and cardiovascular health (1K99ES036311-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10866060. Licensed CC0.

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