# Investigating the role of YAP1 in blood cell specification

> **NIH NIH F31** · TEMPLE UNIV OF THE COMMONWEALTH · 2024 · $37,485

## Abstract

PROJECT SUMMARY/ABSTRACT
Birth defects are the primary cause of infant mortality in the United States, affecting twenty percent of total infant
deaths. Thus, comprehensive insights into the intricate regulation of human development are essential to devise
innovative therapies and prevention strategies to combat birth defects. During embryonic development, a
complex interplay of signaling pathways, effector molecules, and chromatin regulators work together to regulate
lineage-specific gene expression during cell-fate transitions. Gastrulation is required for normal development
and leads to the specification of the three germinal layers; mesoderm, ectoderm, and endoderm. While rare,
disruptions or errors during gastrulation can lead to improper formation of tissues and organs in the developing
fetus. One of the first cell types specified during gastrulation is the blood cell precursors called hemangioblasts,
which derive from the primitive streak (PS). Defects in hemangioblast formation cause disruptions in the normal
development of blood cells, leading to various vascular and hematological disorders. Extensive literature has
shown the cellular mechanisms that determine primitive hematopoietic cells; however, how these precursor cells
are specified during the early stages of PS is understudied. The scientific premise of this proposal is based upon
the repressive transcriptional role of the Hippo signaling effector, Yes-associated Protein 1 (YAP1), on
hemangioblast formation. YAP1 is a known transcriptional effector involved in the Hippo signaling pathway that
has been widely studied for its transcriptional activity in regulating cell growth and proliferation. Our preliminary
data suggest a novel regulatory mechanism of YAP1 mediating the recruitment of Enhancer of zeste homolog 2
(EZH2) to blood lineage genes during hemangioblast formation. Based on these observations, our central
hypothesis is that “YAP1-mediated recruitment of EZH2 on blood lineage genes restrict hemangioblast cell
specification.” We will test our central hypothesis by conducting experiments organized under the following two
specific aims: Aim 1: To investigate the role of YAP1 in hemangioblast formation and primitive streak patterning
at single-cell resolution in vivo and Aim 2. Molecular analysis of YAP1-mediated regulation of blood lineage
genes in hESCs. The proposed studies are significant as they highlight the essential role of YAP1 and EZH2
coordination during blood development. The proposal aims to enhance both technical (single-cell omics and
next-generation sequencing) and conceptual skills in signaling and chromatin dynamics during early
development; this will help promote my Ph.D. training and overall career.

## Key facts

- **NIH application ID:** 10902643
- **Project number:** 1F31HD113419-01A1
- **Recipient organization:** TEMPLE UNIV OF THE COMMONWEALTH
- **Principal Investigator:** Elizabeth Abraham
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $37,485
- **Award type:** 1
- **Project period:** 2024-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10902643

## Citation

> US National Institutes of Health, RePORTER application 10902643, Investigating the role of YAP1 in blood cell specification (1F31HD113419-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10902643. Licensed CC0.

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