Research

Development, regeneration and disease of the uterine epithelium

The endometrium regenerates hundreds of times over a reproductive lifespan. We want to understand the cells and signals that make this possible, and what fails in infertility and endometrial disease.

Five uterine cross-sections over ten days after glandular ablation: lineage-traced glands (green) are lost and regrow within stroma (magenta)
Lineage-traced glands (green) are ablated and regrow over ten days. Mopure et al., bioRxiv 2026.
01 · Gland development

Building the uterine gland

Uterine glands form after birth. Using single-cell atlases of the neonatal mouse uterus, organoids and lineage tracing, we found that a transient epithelial plasticity state defines when glands can be specified. Estrogen receptor alpha, FOXA2 and retinoic acid signaling close this window. Disrupting it causes lasting infertility.

Key papers
  • Rizo et al., bioRxiv 2026
  • Rizo et al., PNAS 2025
  • Spencer et al., PNAS 2023
  • Rizo et al., iScience 2023
Neonatal mouse uterus with forming glandsUterine epithelial organoid
Left: neonatal mouse uterus, CDH1+ epithelium (green) with forming glands. Right: uterine epithelial organoid, a single polarized epithelial layer.
Adult uterus with lineage-traced glands (green) in the surrounding stroma (magenta)
Adult uterus with lineage-traced glands (green) in the surrounding stroma (magenta). Mopure et al., bioRxiv 2026.
Model: luminal epithelium converts to nascent glandular epithelium that matures after ablation
Model of luminal-to-glandular conversion. Mopure et al., bioRxiv 2026.
02 · Regeneration & plasticity

How the endometrium rebuilds

The adult endometrium regenerates with every cycle and after pregnancy. We combine epithelial ablation with transplantation of lineage-labeled organoids. This showed that luminal epithelial cells can acquire glandular identity and function, and that organoid transplantation can restore fertility. Supported by NICHD.

Key papers
  • Mopure et al., bioRxiv 2026
  • Ang et al., bioRxiv 2026 (with McKinley Lab)
03 · Epithelial–stromal crosstalk

Glands, stroma and pregnancy

Glands secrete factors such as LIF that time embryo implantation and support stromal decidualization. We study progesterone receptor in glands, FOXA2 targets and gland–stroma signaling. To do this we built assembloid and polarity-reversed organoid systems that rebuild the epithelial–stromal interface in a dish.

Key papers
  • Bayammagari et al., FASEB J 2025
  • Ahmad et al., Biol Reprod 2026
  • Ahmad et al., Reproduction 2024
  • Kelleher et al., Nat Commun 2018
Mouse endometrial assembloids over four days: organoid epithelium (green) wraps a stromal core (red)
Day 1Day 2Day 3Day 4
Mouse endometrial assembloids: organoid epithelium (green) self-organizes around a stromal core (red) over four days. Ahmad et al., Biol Reprod 2026.
KRT5+ basal-like cells (red) in human endometrial cancer
KRT5+ basal-like cells (red) in human endometrial cancer. Rizo et al., PNAS 2025.
04 · Endometrial disease

From development to disease

Developmental programs give us a map for spotting disease early. Loss of FOXA2 promotes endometriosis, and LIF shows therapeutic promise. Basal-like cells that should not exist in the uterus may flag endometrial cancer. We are extending these studies to human endometrial organoids and assembloids.

Key papers
  • Rahman et al., FASEB J 2025
  • Rizo et al., PNAS 2025
Resources

Models & protocols we share

Prss29-CreAdult uterine gland Cre lineCxcl15-CreGland development Cre lineOrganoid–stroma co-cultureSTAR ProtocolsEndometrial assembloidsMouse & human protocol