Research
Our lab asks how intestinal stem cells drive both repair and development of the gut. Four connected research programs approach this question from different angles, from the inflamed gut of patients with IBD to the developing gut of newborn piglets.
1. E-cadherin: Releasing the Brake on Gut Healing
In IBD, controlling inflammation is often not enough, because the gut lining never fully heals. E-cadherin, the protein that holds intestinal epithelial cells together, acts like a brake on intestinal stem cells: it normally drops briefly during repair so stem cells can rebuild the lining, then returns once healing is complete. We found that in active IBD this brake stays on. Using an inducible knockdown system in colonoids, a new injury model that combines inflammatory cytokines with anoxia, and colonoid transplantation into colitic mice, we showed that briefly releasing E-cadherin activates stem cell and fetal-like regenerative programs and speeds mucosal healing (Girma, Ayansola et al., Am J Physiol Gastrointest Liver Physiol, 2026). With engineers at UMD, we are now developing a “gut-healing smart pill” that pairs an ingestible bioimpedance sensing capsule with mucus-penetrating nanoparticles to deliver this therapy directly to the inflamed gut.
Support: Maryland Stem Cell Research Fund (LAUNCH); NIH R21 (with Drs. Reza Ghodssi and Justin Stine); UMD Grand Challenges Team Grant (with Drs. Ghodssi, Stine, and Katharina Maisel).
2. Priming Stem Cell Therapies to Last: Mesenchymal Stem Cells for IBD
Mesenchymal stem cells (MSCs) can both calm inflammation and repair tissue, but most priming strategies only boost their anti-inflammatory side. We discovered that when human bone marrow MSCs are co-cultured with injured human colonoids, they release far more of the growth factors that activate stem cell regeneration, while keeping their anti-inflammatory output. We are now identifying the factors behind this priming effect and testing primed MSCs in mouse colitis models. To screen these co-cultures at scale, we are building AI-guided imaging and automated analysis with Dr. Po-Yen Chen (UMD Chemical and Biomolecular Engineering).
Support: Maryland Stem Cell Research Fund DISCOVERY award (2025 to 2027), with Dr. Alix Berglund (UMD Veterinary Medicine). Patient-derived colonoids are provided through collaboration with Dr. Shehzad Sheikh (UNC Chapel Hill).
3. Building Better Guts from Birth: The Mesenchymal Niche in Piglet Development
A newborn piglet’s gut is still immature and must mature rapidly around weaning. When this process falters, piglets grow poorly, their gut barrier weakens, and they become more prone to disease. We focus on intestinal mesenchymal stromal cells, the cells beneath the gut lining that direct how epithelial cells grow, specialize, and form a barrier. Using transcriptomic profiling, we have mapped how this stromal niche remodels during early postnatal life (Ayansola & Jin, Front Cell Dev Biol, 2026). We pair porcine organoids with stromal cells and AI-guided imaging to screen feed additives, such as butyrate, that activate the niche, then test promising candidates in pre-weaning piglets. Because piglets closely resemble human infants, this work also offers a model for human infant gut development.
Support: Maryland Agricultural Experiment Station. Collaborators: Dr. Samer El-Kadi (Virginia Tech) and Dr. Mohamed Salem (UMD).
4. Protecting the Gut Barrier: Larazotide Acetate and Ischemic Injury
When blood flow to the gut is disrupted, the tight junctions that seal the intestinal lining fail. This ischemic injury contributes to necrotizing enterocolitis in premature infants and ischemic colitis in adults, and no targeted therapy exists. We found that the therapeutic peptide larazotide acetate protects the barrier during anoxia and reoxygenation injury by blocking the contraction signal that pulls cells apart (Kim et al., Biomedicines, 2025). This work continues with industry partners advancing larazotide acetate toward clinical development.
Collaborations
Our organoid and animal models support research across UMD and beyond, including avian enteric virus infection (Drs. Andrea Broadbent and Margaret Scull), intestinal immunology (Dr. Zhengguo Xiao), the gut microbiome (Dr. Mohamed Salem), and the gut-placenta axis (Dr. Seo). Industry partners include Caleo Biotechnologies, with whom we received a Maryland Stem Cell Research Fund Commercialization award to advance patient-derived organoid platforms for precision therapy in IBD.