# Endometrial immune microenvironment dysfunction in endometriosis pathobiology

> **NIH NIH K99** · STANFORD UNIVERSITY · 2024 · $131,085

## Abstract

PROJECT SUMMARY
Endometriosis, a debilitating chronic disease, affects around 10% of reproductive age women worldwide,
severely impacting quality-of-life. Unfortunately, there is often a decade-long delay from first symptom onset to
definitive diagnosis, underscoring the urgent need for improved earlier diagnostics. Evidence suggests that local
endometrial immune microenvironment (EIM) dysregulation may play a key factor in endometriosis pathobiology.
Even though uterine NK (uNK) cells are the predominant cytolytic lymphocyte in the EIM, they have been
surprisingly understudied in endometriosis. The objective of this proposal is to gain a better understanding of the
contribution of uNK cells to endometriosis and to identify non-invasive menstrual blood (MB) biomarkers that can
be leveraged for diagnosis. I hypothesize that defective cytolysis of endometrial stromal cells by dysregulated
uNK cells contributes to an abnormal tissue environment in endometriosis. The work in this proposal will be
completed at Stanford University School of Medicine in Dr. Gaudilliere’s laboratory (primary mentor) with
guidance from an interdisciplinary mentoring team at UCSF (Dr. Giudice, Dr. Sirota) and Duke University (Dr.
Coyne). A rigorous research training plan is proposed that harnesses cutting-edge high-dimensional single-cell
suspension and spatial immune profiling, sparse machine learning methods, and ex vivo assembloid modeling.
Aim 1 (K99) will characterize the inhibitory/activating receptor repertoire and functional capacity of uNK cells of
women with and without endometriosis (scRNAseq and mass cytometry). In addition, examining the spatial
organization of the EIM will provide crucial insight into microenvironmental interactions that underlie immune
responses in healthy and diseased endometrium (imaging mass cytometry). This aim builds on my current
expertise in human reproductive immunology and multi-parameter approaches and is a continuation of prior work
showing that uNK cells predominate in the EIM and exhibit a tissue-specific receptor profile. In Aim 2, an
innovative MB immunoassay will be established on the mass cytometry platform (K99) by discerning the
similarities and disparities between biopsy and MB-derived uNK cells. In the R00 phase, high-dimensional
predictive modeling will identify uNK cell features in MB that accurately classify endometriosis versus control. In
Aim 3, through Dr. Coyne’s training (K99), endometrial assembloids derived from primary MB-derived
endometrial cells will be established to replicate the EIM ex vivo. In the R00 phase, uNK cells will be incorporated
into this assembloid model to further investigate uNK-mediated mechanisms in abnormal endometrial tissue. In
summary, the proposed studies will uncover fundamental uNK cell mechanisms that contribute to endometriosis
pathobiology and establish a foundation for developing non-invasive diagnostics. The training, approach, and
results generated will offer a unique framewor...

## Key facts

- **NIH application ID:** 10950247
- **Project number:** 1K99HD115829-01
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Dorien Feyaerts
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $131,085
- **Award type:** 1
- **Project period:** 2024-09-05 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10950247

## Citation

> US National Institutes of Health, RePORTER application 10950247, Endometrial immune microenvironment dysfunction in endometriosis pathobiology (1K99HD115829-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10950247. Licensed CC0.

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