# Deciphering Principles of Human Embryonic Patterning in Development and Disease

> **NIH NIH DP2** · YALE UNIVERSITY · 2022 · $1,507,500

## Abstract

Project Summary/Abstract
Fundamental questions in developmental biology revolve around understanding the sequence of molecular and
cellular events that regulates lineage specification and differentiation. Nowhere is this more poorly understood
than in the early human embryo, which remains experimentally intractable for technical and ethical reasons past
the onset of gastrulation - the point when the three major germ layers of the human body are specified within the
embryonic epiblast tissue. Myself and others have previously developed stem cell-based systems that
recapitulate key aspects of 3-dimensional (3D) mammalian development in vitro, paving the way to a more
complete understanding of the specific steps that govern embryonic development. Here, I propose an innovative
new experimental approach, using human pluripotent stem cells (hPSCs), combined with cutting-edge
bioengineering technologies for a controllable, efficient and scalable modeling of human epiblast development
in vitro. This model will permit studying the human germ layer differentiation trajectory and temporal dynamics
in the correct 3D-conformation. I will combine state-of-the-art tools in genetics, imaging, and single-cell multi-
omics in tandem with high-throughput computational analyses to define the key molecular and cellular events
that regulate developmental patterning under different conditions. I will further investigate how these events are
controlled by cellular metabolism and nutrient availability, which has important implications for understanding the
early embryonic origin of numerous human diseases. My proposal will open up a completely new and powerful
experimental paradigm to dissect the fundamental, inter-connected, principles of human developmental genetics
at early embryonic stages that are otherwise inaccessible. This new knowledge will also directly inform efforts to
efficiently generate mature tissues and cell types from stem cells for disease modeling and cell therapies.
Ultimately, these findings will be critical for possible prevention of adverse pregnancy outcomes, offering a
unique opportunity to understand the cellular and molecular mechanisms behind developmental disorders and
congenital pathologies.

## Key facts

- **NIH application ID:** 10471048
- **Project number:** 1DP2HD112040-01
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Berna Sozen
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,507,500
- **Award type:** 1
- **Project period:** 2022-09-15 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10471048

## Citation

> US National Institutes of Health, RePORTER application 10471048, Deciphering Principles of Human Embryonic Patterning in Development and Disease (1DP2HD112040-01). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10471048. Licensed CC0.

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