High dimensional and functional analysis of uterine natural killer cells in endometriosis
Active Project Grant Awarded Last action
- Award ID
- F30HD118748
- Recipient
-
The Leland Stanford Junior University UEI HJD6G4D6TJY5
- Awarding agency
-
National Institute of Child Health and Human Development
National Institutes of Health, Department of Health and Human Services
- Obligated
- $43,061
Award facts
- Assistance listing
- 93.865 Child Health and Human Development Extramural Research
- Completion date 0% complete
- Place of performance
- Palo Alto, CA 94304, USA
Award details come from USAspending.gov.
Description
- Abstract
- Endometriosis (EM) is a chronic pain disorder characterized by growth of endometrial lesions in the peritoneum. By conservative estimates, EM impacts over 190 million people with uteri worldwide, has a 7-11 year latency between symptom onset and diagnosis, and costs the united states nearly $120 billion annually in direct healthcare costs and productivity loss. Less invasive diagnostic measures for EM are needed. Though EM manifests in peritoneal lesions, EM pathophysiology is thought to begin within the eutopic endometrium (EUE), where the immune microenvironment may contribute to the ability of endometrial tissue to persist and evade clearance in the peritoneum upon retrograde menstruation-mediated translocation. Uterine natural killer (UNK) cells dominate the uterine mucosal immune landscape and modulate endometrial homeostasis via modulation of immune and stromal cell growth and differentiation. UNK subsets are phenotypically perturbed in the eutopic endometrium of patients with EM, presenting as a shift towards immaturity and non-cytotoxicity. This perturbation is thought to promote persistence and evasion of clearance of translocated endometrium in the peritoneum. However, prior work decouples UNK phenotype from UNK spatial and functional interactions with endometrial stromal and immune cells, leaving the latter unexplored. UNK spatial and functional dynamics could contribute to needed early and non-surgical biopsy-based diagnostics for EM. I propose to determine the role of UNK cells in the pathogenesis of endometriosis by combining spatial assessment of the endometrial cellular landscape using high-dimensional imaging mass cytometry (IMC) with in vitro functional analysis of UNK cells in endometriosis. I will first deeply spatially profile immune and stromal phenotypes and interactions in eutopic endometrial biopsies of participants with and without EM, which will be the first spatial proteomic characterization of both normal and endometriosis patient endometrium (aim 1). In addition to the identification of cell and neighborhood-based features that contribute to the pathobiology of endometriosis, I will computationally analyze this data by developing and modeling functional and spatial features using recently developed biocomputational and machine-learning methods for the identification of biomarkers of clinical significance. To connect static features in preserved tissue to cell activities in live tissue, I will isolate UNK cells from endometrial biopsies for receptor and subset profiling, killing ability, and cytokine release when CO-cultured with autologous stromal cells (AIM2). I will also analyze the impact of UNK cytokine release on endometrial stromal progesterone receptor to delineate UNK cell contribution to progesterone resistance in endometriosis. This work harnesses expertise in high-dimensional spatial proteomics and machine learning (gaudillière lab), and NK cell biology and functional characterization (blish lab). With the joint mentorship of DR. Blish and gaudillière, the rigorous training environment of the stanford mstp, and the support of this fellowship, I will develop into a creative physician- scientist at the forefront of disease-focused reproductive immunology investigation.
Quick answers
Who received award F30HD118748?
F30HD118748 was awarded to The Leland Stanford Junior University by National Institute of Child Health and Human Development (National Institutes of Health) on December 1, 2026.
How much is award F30HD118748 worth?
$43,061 has been obligated on F30HD118748.
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