# Endothelial regulation of the blood-placental barrier

> **NIH NIH K99** · UNIVERSITY OF PENNSYLVANIA · 2024 · $132,705

## Abstract

Project Summary
Placental vasculature is critical for the exchange of oxygen, nutrients, and waste products between
maternal and fetal circulation. Failure to establish this vascular network is associated with fetal growth
restriction and maternal cardiovascular pathologies. However, the signaling pathways that regulate
placental vascular growth and function remain largely unknown. My long-term goal is to elucidate the
cellular and molecular basis underlying placental vascular network formation and function at the blood-
placental barrier, as well as how the placental endothelium affects fetal growth and maternal
cardiovascular health. By utilizing a new genetic tool, the Hoxa13Cre line, that specifically targets
placental vasculature but not vasculature in the embryo proper or yolk sac, I have found that placental
endothelial-specific deletion of transcription regulators YAP/TAZ results in embryonic lethality and
compromised placental vasculature. I propose to investigate the molecular basis for placental vascular
growth and function by leveraging unique genetic tools, advanced imaging, and single-cell genomics
(Aim 1). In addition, I will explore the roles of the placental endothelium in maternal-fetal exchange by
combining mouse genetics and proteomic analysis (Aim 2). These lines of investigation will reveal
transcriptional and epigenetic mechanisms by which placental vasculature grows and offer insights into
the roles of the endothelium in the blood-placental barrier. The proposed studies complement my prior
skills while acquiring new training in placental biology, single-cell technologies, and proteomics analysis
to establish a strong foundation to build an independent research career. With a world-class team of
mentors and collaborators with expertise in placental biology, cardiovascular metabolism, and
bioinformatics to ensure exceptional guidance and a supportive, stimulating training environment at the
University of Pennsylvania, I am ideally positioned to fully develop my technical skills and knowledge
in placental vascular biology. Together, the proposed research and career development activities will
be critical for me to develop an independent research program centered around understanding
endothelial regulation in the blood-placental barrier.

## Key facts

- **NIH application ID:** 10947771
- **Project number:** 1K99HL175038-01
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Siqi Gao
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $132,705
- **Award type:** 1
- **Project period:** 2024-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10947771

## Citation

> US National Institutes of Health, RePORTER application 10947771, Endothelial regulation of the blood-placental barrier (1K99HL175038-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10947771. Licensed CC0.

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