# Invasive trophoblast cell differentiation

> **NIH NIH F32** · UNIVERSITY OF KANSAS MEDICAL CENTER · 2024 · $73,828

## Abstract

PROJECT SUMMARY
In the early stages of human pregnancy, cells from the developing placenta, termed extravillous trophoblast
(EVT) cells, must interact with the uterus. In other species including the rat, this special class of trophoblasts are
generically termed invasive trophoblast cells. The interaction between invasive trophoblast/EVT cells and the
uterus results in the necessary remodeling of spiral arteries to meet the increased demand of blood flow and
oxygen during pregnancy. Once remodeled, these arteries will integrate into the uterus to function in transporting
nutrients and waste to and from the fetus through the maternal bloodstream. Importantly, differentiation into these
specialized trophoblast cell types requires suppression of pathways essential for maintaining the trophoblast cell
stem state and activation of the invasive/EVT cell differentiation program. In this project, we investigate roles for
the leukemia inhibitory factor (LIF) and signal transducer and activator of transcription 3 (STAT3) pathway in the
regulation of invasive/EVT cell development. Roles for LIF/STAT3 regulatory networks in human trophoblast
stem cell models are the focus of Specific Aim 1. In Specific Aim 2, we will leverage a Stat3 conditional rat model
to investigate STAT3 effects on the development and functionality of the invasive trophoblast cells at the uterine-
placental interface. Experimentation includes genome-wide analyses of the transcriptome and the chromatin
landscape. Completion of this research project will facilitate the discovery of molecular controllers responsible
for regulating invasive/EVT cell lineage as well as create a platform for understanding the pathogenesis of early
pregnancy loss. In addition, this proposal will provide the postdoctoral trainee with the mentorship, training, and
skills required to become a successful independent investigator dedicated to human fertility research.

## Key facts

- **NIH application ID:** 10999051
- **Project number:** 1F32HD116506-01
- **Recipient organization:** UNIVERSITY OF KANSAS MEDICAL CENTER
- **Principal Investigator:** Savannah Speckhart
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $73,828
- **Award type:** 1
- **Project period:** 2024-08-12 → 2027-08-11

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10999051

## Citation

> US National Institutes of Health, RePORTER application 10999051, Invasive trophoblast cell differentiation (1F32HD116506-01). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10999051. Licensed CC0.

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