Our long-term research goal is to understand how intestinal stem cells (ISCs) drive both repair and development of the gut, and to apply that biology to two problems at once: mucosal healing in inflammatory bowel disease (IBD) and gut maturation in neonatal piglets. We study the interplay between the apical junctional complex, ISCs, and the mesenchymal stromal niche using human, mouse, and porcine intestinal organoids, genetically engineered mouse models, and piglet studies. Working with engineers, immunologists, virologists, and physicians, we aim to move these discoveries toward real therapeutic and agricultural applications.
E-cadherin: Releasing the Brake on Gut Healing. In IBD, calming inflammation is not enough. Up to 80% of Crohn's disease patients and 20 to 30% of ulcerative colitis patients eventually need surgery because the gut lining never fully heals. We found that E-cadherin, the core adherens junction protein, acts as a dynamic switch for ISC-driven repair: it transiently drops during healthy regeneration to let stem cells rebuild the epithelium, then returns once healing is complete. In active IBD, this brake stays engaged and keeps repair switched off. Using human and mouse organoids and ISC-specific E-cadherin knockout mice, we showed that briefly releasing E-cadherin activates pro-regenerative Wnt and Hippo signaling, restores regeneration, and accelerates mucosal healing without lasting barrier damage (Am J Physiol Gastrointest Liver Physiol, 2026). Together with engineering collaborators, we are now developing a gut-healing smart pill that delivers E-cadherin-targeted therapy directly to the inflamed gut lining.
Priming Mesenchymal Stem Cells (MSCs) for IBD Therapy. MSCs are both anti-inflammatory and tissue-repairing, but most priming strategies developed so far boost only their immunomodulatory side, leaving their regenerative potential largely untapped. We discovered that co-culturing human bone marrow-derived MSCs with injured human colonoids, rather than with generic inflammatory cytokines, markedly increases their release of growth factors that directly activate ISC regeneration while preserving their anti-inflammatory output. Supported by the Maryland Stem Cell Research Fund (MSCRF) Discovery Program and in partnership with Dr. Alix Berglund (Department of Veterinary Medicine), we are identifying the factors that drive this dual priming effect and testing primed MSCs in murine colitis models. With Dr. Po-Yen Chen (Chemical and Biomolecular Engineering), we are also building AI-guided imaging and analysis of organoid co-cultures.
Building Better Guts from Birth: The Mesenchymal Niche in Piglet Development. The neonatal piglet gut must mature rapidly in the days around weaning, and when that process falters, piglets grow poorly, their gut barrier weakens, and they become more prone to disease. We focus on intestinal mesenchymal stromal cells (iMCs), the stromal cells beneath the epithelium that direct how epithelial cells grow, differentiate, and form a barrier. We showed that the iMC niche is remodeled in an age-dependent manner during the pre-weaning period, shifting from supporting epithelial expansion to promoting differentiation, with a calcium-associated transitional stromal state emerging along the way (Front Cell Dev Biol, 2026). We pair enteroid and iMC co-cultures with AI-guided organoid screening to identify feed additives, such as butyrate, that activate iMCs at the right developmental stage, and then validate promising candidates in pre-weaning piglets. Because piglets are physiologically similar to human infants, this stroma-targeted, antibiotic-free strategy also offers a model for human infant gut development.
Protecting the Gut Barrier: Larazotide Acetate and Ischemic Injury. Building on our earlier work on tight junctions, we found that the therapeutic peptide larazotide acetate protects the intestinal barrier during anoxia/reoxygenation injury through multiple cellular mechanisms, including inhibition of myosin light chain kinase (Biomedicines, 2025). This work, relevant to necrotizing enterocolitis in premature infants and ischemic colitis in adults, continues through an industry collaboration advancing larazotide acetate toward clinical development.
Collaborative Project: Ingestible Bioimpedance Capsules and a Gut-Healing Smart Pill. In collaboration with Drs. Reza Ghodssi and Justin Stine in the MATRIX Lab and Dr. Katharina Maisel in Bioengineering at UMD, we are developing ingestible devices to monitor and treat the gut. Our wireless bioimpedance-sensing capsule measures site-specific mucosal permeability in vivo and accurately detected inflammation-associated permeability changes in a rat colitis model (Microsystems & Nanoengineering, 2025; Device, 2026). Supported by an NIH R21 award and a UMD Grand Challenges 2.0 Team Grant, we are now pairing this capsule with mucus-penetrating nanoparticles to create a smart pill that can both monitor and treat IBD.
A Resource for the Research Community. Our organoid and animal systems also support collaborative studies of avian enteric viral infection, intestinal immune cells, the gut microbiome, and the gut-placenta axis, as well as industry partnerships on patient-derived organoid platforms for precision IBD therapy.
† Trainees mentored in the Jin Lab; * equal contribution. Full list: ORCID 0000-0003-2450-9330