# Epigenetic determinants of competence for germ line specification during human embryonic development

> **NIH NIH K08** · BETH ISRAEL DEACONESS MEDICAL CENTER · 2022 · $164,860

## Abstract

Project Summary
CANDIDATE. I am a physician and Instructor in the Division of Reproductive Endocrinology and Infertility at
Beth Israel Deaconess Medical Center (BIDMC). A K08 Award will provide me with the necessary training and
experience to become an independent investigator in germ cell (GC) biology, with a focus on the gene
regulatory networks underlying human gametogenesis.
BACKGROUND. How a small subset of cells in the developing human and non-human primate embryo
acquires competency to form the germ line and ultimately mature into functional gametes while maintaining its
potential for pluripotency is among the least understood questions in biology. In particular, the gene regulatory
networks and epigenetic remodeling, which govern competence for the GC fate during specification of early
(primordial) germ cells (PGCs) in the peri-gastrulating period, remain unknown. Knowledge of the underlying
mechanisms will allow the development of more efficient differentiation protocols for GCs from pluripotent stem
cells (PSCs) in vitro. In addition, it will allow the investigation of the link between epigenetic dysregulation
during GC specification and critical human disorders such as pregnancy loss, congenital defects and common
late-onset diseases such as infertility, diabetes, drug addiction and cancer.
RESEARCH. The objective for this K08 is to identify and validate the key gene regulatory elements (GREs)
governing induction of competence for the GC fate and the differentiation of PGCs during cynomolgus
gastrulation. Our central hypothesis is that epigenetic priming of key GREs in incipient mesoderm mediates
developmental competence during germ lineage specification from the pluripotent state. This research will
pursue two specific aims: (1) to identify putative GREs underlying developmental competence for the GC fate
through epigenetic footprinting (2) to identify the subset of these GREs functioning as key determinants of GC
competence and differentiation using massively parallel reporter assays (MPRA) and CRISPR epigenome
editing mediated loss of function experiments. In the future, these results will provide the platform to use
epigenome editing as a tool to improve the efficiency of GC specification, for trans-differentiation of GCs from
somatic cells and to study the effect of epimutations on developmental outcomes in GCs and embryos using
animal models.
MENTORING. My primary mentor, Dr. Kevin Eggan, is an expert in stem cell biology at the Harvard Stem Cell
Center. I have assembled a multi-disciplinary mentoring team across the Harvard network: Dr. Alex Meissner
(an expert in epigenetics and epigenomics), Dr. Steve McCarroll (a leader in genomics and bioinformatics).
TRAINING. The research objectives are supported by a training plan that includes hands-on lab training as
well as formal and hands-on didactics in bioinformatics and the analysis of large genomic datasets alongside a
strong institutional commitment at BIDMC and the grant revie...

## Key facts

- **NIH application ID:** 10371226
- **Project number:** 5K08HD098556-03
- **Recipient organization:** BETH ISRAEL DEACONESS MEDICAL CENTER
- **Principal Investigator:** Werner Neuhausser
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $164,860
- **Award type:** 5
- **Project period:** 2020-04-21 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10371226

## Citation

> US National Institutes of Health, RePORTER application 10371226, Epigenetic determinants of competence for germ line specification during human embryonic development (5K08HD098556-03). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10371226. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*