Dissecting the role of epithelial-fibroblast crosstalk in endometriosis-associated infertility
Active Project Grant Awarded Last action
- Award ID
- F30HD123655
- Recipient
-
University Of Connecticut Health Center UEI H6D6JMXJXDE6
- Awarding agency
-
National Institute of Child Health and Human Development
National Institutes of Health, Department of Health and Human Services
- Obligated
- $55,114
Award facts
- Assistance listing
- 93.865 Child Health and Human Development Extramural Research
- Completion date 0% complete
- Place of performance
- Farmington, CT 06030, USA
Award details come from USAspending.gov.
Description
- Abstract
- Endometriosis is a chronic inflammatory condition affecting 10-15% of women, causing significant pelvic pain and infertility. While the normal endometrium relies on tightly regulated, spatial WNT-mediated crosstalk between epithelial and fibroblast cells to establish a receptive lining, this process is disrupted in endometriosis. In diseased tissue, fibroblasts are thought to drive pathology by inducing aberrant WNT signaling and preventing the endometrium from properly transitioning into a receptive state. The goal of this proposal is to leverage a mechanistic understanding of this spatial epithelial-fibroblast crosstalk to develop new therapeutic strategies for endometriosis-associated infertility. My preliminary spatial transcriptomic data reveal that WNT ligands and antagonists form specific expression gradients in fibroblasts, a cell type disrupted in endometriosis. I hypothesize that this dysregulated WNT- mediated crosstalk drives abnormal epithelial differentiation, thereby impairing endometrial receptivity. Aim 1 will characterize the epithelial response to endometriosis-derived fibroblasts using patient-derived 3D CO-cultures and single-cell RNA sequencing. I will subsequently use crispr-CAS9 gene editing to systematically demonstrate the contribution of specific WNT genes to the infertility phenotype. Aim 2 will spatially validate these interactions in human pre-receptive and receptive endometrial biopsies using high-resolution spatial transcriptomics to profile cell neighborhoods and signaling niches. Successful completion of these aims will elucidate the pathological niches unique to endometriosis-associated infertility and identify potential therapeutic targets. However, this F30 fellowship will ultimately provide me with a unique research framework to elucidate mechanistic insights across many gynecological conditions through translatable skills in advanced in vitro organ modeling and single-cell transcriptomics/spatial omics. Therefore, this training is imperative for my development as a future independent physician-scientist who aims to address the bench to bedside gaps in women's health.
Quick answers
Who received award F30HD123655?
F30HD123655 was awarded to University Of Connecticut Health Center by National Institute of Child Health and Human Development (National Institutes of Health) on February 1, 2027.
How much is award F30HD123655 worth?
$55,114 has been obligated on F30HD123655.
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