# Hippo Signaling Effector and Placentation

> **NIH NIH R01** · UNIVERSITY OF KANSAS MEDICAL CENTER · 2021 · $455,266

## Abstract

Abstract
Early pregnancy loss affects 15-20% of implantation-confirmed pregnancies. Majority of these pregnancy losses
occur during first trimester and defective development of trophoblast progenitors, which assures embryo
implantation and placentation, is one of the leading causes for early pregnancy loss. However, we have a poor
understanding of molecular mechanisms that regulate trophoblast progenitor self-renewal, differentiation and
function in early postimplantation embryos. Our published and preliminary studies establish that hippo signaling
effector, transcription factor TEAD4 is conserved in trophoblast progenitors across mammalian species and is a
critical regulator to specify and maintain the trophoblast cell lineage during early mammalian development. The
overarching goal of this proposal is to further define TEAD4-mediated conserved molecular mechanisms that are
specifically involved in regulating trophoblast progenitor self-renewal and differentiation during post-implantation placenta
development. In addition, we will also test whether alteration of those mechanisms is associated with recurrent
pregnancy loss (RPL).
Three specific aims are proposed. Aim 1 will study mutant mouse models to test the hypothesis that TEAD4
regulates trophoblast stem-like progenitor cell (TSPC) self-renewal in early postimplantation embryos.
Aim 2 will test the hypothesis that cell-autonomous function of TEAD4 in lineage-specific trophoblast
progenitors ensures proper development of differentiated trophoblast cells and formation of the maternal-fetal interface.
 In Aim 3, we will test functional importance of TEAD4 in human primary cytotrophoblasts (CTBs) and CTB-
derived human trophoblast stem cells (TSCs). We will also recruit patients with known history of recurrent pregnancy
loss (RPL) to isolate CTBs and establish patient-specific TSCs. The goal is to test the hypothesis that TEAD4 regulates
self-renewal of CTB progenitors in a developing human placenta and defective function of TEAD4 is the molecular cause
for a subset of unexplained (idiopathic) RPLs.

## Key facts

- **NIH application ID:** 10136059
- **Project number:** 5R01HD101319-02
- **Recipient organization:** UNIVERSITY OF KANSAS MEDICAL CENTER
- **Principal Investigator:** Soumen Paul
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $455,266
- **Award type:** 5
- **Project period:** 2020-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10136059

## Citation

> US National Institutes of Health, RePORTER application 10136059, Hippo Signaling Effector and Placentation (5R01HD101319-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10136059. Licensed CC0.

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