# Elucidation of the upstream transcription factors controlling preeclampsia-specific gene expression using human trophoblast stem cells as a model system

> **NIH NIH R21** · UNIVERSITY OF TEXAS AT AUSTIN · 2024 · $191,965

## Abstract

PROJECT SUMMARY
Preeclampsia (PE) is a relatively common pregnancy disorder that originates from the placenta. It affects
up to 8% of all human pregnancies and causes various maternal and fetal health problems, including
maternal vascular dysfunction, proteinuria, and hypertension as well as growth restriction and preterm birth
of the baby. It has no cure other than the delivery of the baby and can lead to eclampsia, which may result
in death via stroke. It is generally accepted that defects in trophoblast lineage development, critical for
proper implantation and placentation, are the leading cause of PE. However, the underlying molecular
mechanisms of PE have not been well understood. While many genes upregulated or downregulated in
PE have been identified by global gene expression analysis, upstream key transcription factors (TFs)
responsible for the PE-specific gene expression programs (PE-driver TFs) and their action mechanisms
have not yet been described. Furthermore, how such PE-driver TFs disrupt normal trophoblast lineage-
specific gene regulatory networks remains unknown. The objectives of the proposed studies are to identify
transcriptional and epigenetic regulators modulating PE-specific gene expression programs and to
understand their action mechanisms by utilizing recently established human trophoblast stem cells (TSC)
and their in vitro differentiation into syncytiotrophoblast (ST) and extravillous trophoblast (EVT) as a model
system. Our preliminary studies suggested that the untimely or sustained upregulation of sequence-
specific TFs may trigger abnormal expression of target genes known to be PE-specific, which may lead to
impaired ST/EVT differentiation and, ultimately, PE phenotypes. To understand the molecular basis of PE,
we will 1) identify and functionally validate putative PE-driver TFs which can induce PE-specific gene
expression programs by utilizing human TSC differentiation as a model and 2) understand the regulatory
mechanisms PE-driver TFs by mapping their downstream target genes and interaction partner proteins.
The successful completion of this proposal will provide us with new models for studying the
pathophysiology of human PE, illumination of molecular regulatory mechanisms underlying PE, and thus
enhance our ability to generate novel diagnostic tools and therapeutics to improve healthcare for both the
women with PE and their babies in the near future.

## Key facts

- **NIH application ID:** 10870500
- **Project number:** 1R21HD115116-01
- **Recipient organization:** UNIVERSITY OF TEXAS AT AUSTIN
- **Principal Investigator:** Jonghwan Kim
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $191,965
- **Award type:** 1
- **Project period:** 2024-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10870500

## Citation

> US National Institutes of Health, RePORTER application 10870500, Elucidation of the upstream transcription factors controlling preeclampsia-specific gene expression using human trophoblast stem cells as a model system (1R21HD115116-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10870500. Licensed CC0.

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