# Oxytocin-mediated calcium signaling in physiologic uterine contractility and uterine atony

> **NIH NIH K23** · STANFORD UNIVERSITY · 2024 · $165,672

## Abstract

Project summary
Postpartum hemorrhage (PPH) is the leading global cause of maternal morbidity and mortality. Uterine atony,
insufficient uterine contractility after placental delivery, causes 80% of PPH. Oxytocin is the medical standard of
care for prophylaxis and first line treatment of PPH. However, the mechanism whereby oxytocin causes uterine
contractility remains incompletely understood. There is a critical need to determine (1) how oxytocin causes
uterine contractility, and (2) the cellular and molecular mechanisms that underlie compromised oxytocin response
in uterine atony. Such knowledge is integral to the discovery of novel, targeted treatments for uterine atony.
Recent data in mice highlight a role for the Transient Receptor Potential Vanilloid 4 (TRPV4) channel in oxytocin-
mediated uterine contractility. To address human uterine contractility, Dr. Ansari proposes innovative
translational research using uterine tissue and derived smooth muscle cell cultures from cohorts of parturients
with normal contractility and uterine atony. She will uncover molecular and cellular mechanisms of human uterine
contractility in normal physiology versus uterine atony, define the role of the TRPV4 channel, and explore
whether pharmacologic activation of TRPV4 may represent a novel uterotonic strategy. The first aim centers on
normal, physiologic contractility, and the second on the pathophysiology of uterine atony: Aim 1) Determine the
functional relationship between oxytocin and TRPV4 and the mechanisms of TRPV4 activation in normal uterine
contractility; and Aim 2) Define TRPV4-dependent and TRPV4-independent mechanisms underlying uterine
atony through cellular and molecular assays including single nuclei RNA sequencing.
Dr. Ansari’s training will be conducted under the experienced mentorship of Dr. David N. Cornfield (smooth
muscle biology, calcium signaling, and single cell transcriptomics), and Dr. Virginia Winn (maternal fetal
medicine, basic and translational research in obstetrics), in conjunction with expert advisors in TRPV channel
biology, biobanking, uterine atony, and PPH. This training will be enhanced by the Chan Zuckerberg Biohub
Physician Scientist Fellowship program, advanced coursework in translational medicine, single cell RNA
sequencing, and research laboratory management, and the supportive infrastructure of Stanford’s Maternal-
Fetal Medicine and Obstetric Anesthesia Divisions. Through this K23, Dr. Ansari will obtain broad-based
knowledge and skills in laboratory research including advanced experiential training in uterine smooth muscle
biology, calcium signaling, and single cell transcriptomics. These skills will equip her to pursue her long-term
goal to develop an independent research career identifying new therapeutic targets for uterine atony at the bench
with the ultimate goal of translating discoveries to clinical care to address PPH.

## Key facts

- **NIH application ID:** 10949817
- **Project number:** 1K23HD115837-01
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Jessica Ansari
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $165,672
- **Award type:** 1
- **Project period:** 2024-07-15 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10949817

## Citation

> US National Institutes of Health, RePORTER application 10949817, Oxytocin-mediated calcium signaling in physiologic uterine contractility and uterine atony (1K23HD115837-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10949817. Licensed CC0.

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