Our long-term research objective is to elucidate the critical mechanisms governing intestinal epithelial homeostasis, regeneration, and development. We focus on the interplay between the apical junctional complex, intestinal stem cells (ISCs), and the stromal microenvironment to understand the pathogenesis of gastrointestinal diseases such as inflammatory bowel disease (IBD) and to improve intestinal health in neonatal development.
Role of E-cadherin as a Dynamic Switch for Intestinal Stem Cell Regeneration. Mucosal healing is a critical therapeutic goal in IBD, yet the specific role of adherens junctions (AJs) in this process has remained elusive. We are investigating how E-cadherin, a core AJ protein, functions as a dynamic switch during the regeneration phase. Our recent findings suggest that transient downregulation of E-cadherin is essential for initiating effective epithelial repair. Using an inducible knockdown model in colonoids, we demonstrated that temporary reduction of E-cadherin promotes a stem-like, hyperproliferative state by activating Wnt and Hippo signaling pathways. Conversely, persistent loss leads to barrier dysfunction. We propose that precisely modulating this "switch"—temporarily suppressing E-cadherin to boost regeneration and then restoring it for maturation—could be a novel therapeutic strategy to accelerate mucosal healing in IBD patients.
Priming Mesenchymal Stem Cells (MSCs) for IBD Therapy While Mesenchymal Stem Cells (MSCs) show promise for treating IBD due to their immunomodulatory properties, their clinical efficacy remains variable. This project aims to enhance the therapeutic potential of human bone marrow-derived MSCs (hBM-MSCs) by focusing on their ability to directly support ISC regeneration. We are developing novel priming strategies to boost the secretion of therapeutic factors that promote both mucosal healing and immunomodulation. By identifying specific priming candidates through proteomic analysis of injured colonoids, we aim to generate "super-charged" MSCs that can effectively repair the damaged intestinal barrier and suppress inflammation in murine colitis models.
Dynamic Reprogramming of Intestinal Mesenchymal stromal Cells (iMCs) in Pig Development The neonatal porcine intestine undergoes rapid remodeling, a process critically regulated by the underlying stroma. Our research has identified that intestinal mesenchymal stromal cells (iMCs) undergo dynamic molecular reprogramming during the pre-weaning period to direct epithelial development. We discovered that iMSCs shift from supporting epithelial expansion (Day 0) to promoting differentiation (Day 7) through distinct signaling mechanisms, including a surge in calcium signaling and glucose metabolism at Day 7. This project aims to leverage these stage-specific iMSC signatures to develop targeted nutritional interventions—such as specific feed additives—that optimize gut maturation and growth performance in piglets.
Collaborative Project: Ingestible Bioimpedance Capsules for Monitoring Gut Health. In collaboration with Drs. Reza Ghodssi and Justin Stine in the MATRIX Lab at the UMD, we are developing non-invasive technologies to monitor intestinal health. We are validating a wireless ingestible bioimpedance sensing capsule capable of measuring mucosal permeability in vivo. Unlike traditional endoscopy, this device can continuously monitor site-specific tissue properties throughout the GI tract. Our recent work demonstrated the capsule's ability to accurately detect permeability changes associated with inflammation in rat colitis models, offering a promising new tool for the real-time diagnosis and monitoring of IBD progression.
ANSC 445: Comparative Digestive Pathophysiology
ANSC 645: Advanced Studies in Comparative Digestive Pathophysiology
ANSC 401: Animal Growth and Development for Production Agriculture
Discovery Program, Maryland Stem Cell Research Fund, 2025-2027
co-PI: Grand Challenge Team Project Grant, FY 2023-26
LAUNCH program, Maryland Stem Cell Research Fund, 2021-2023
Maryland Agricultural Experiment Station (MAES) Competitive Grant Program, 2020-2021, 2023- 2024
Innovate Biopharmaceuticals, Inc. 2019-2021
Pilot/Feasibility Grant, Center for Gastrointestinal Biology and Disease, 2017-2018