Inflammatory Bowel Disease (IBD) causes chronic intestinal inflammation; however, one of the hallmarks of IBD is pathological matrix remodeling of the intestinal wall, which manifests as either intestinal stricturing (fibrosis) or fistulae formation (degradation). This project uses a combination of modifiable, synthetic 3D matrices and human iPSC-derived intestinal organoids, which contain both epithelial and mesenchymal cells to create a reductionist model of the intestine. Our goal is to fundamentally understand how pathological matrix remodeling in the mesenchyme contributes to inflammatory-like phenotypes in the epithelium, potentially leading to the discovery of targets that could be exploited therapeutically.
Ferreira SA, Motwani MS, Faull PA, Seymour AJ, Yu TTL, Enayati M, Taheem DK, Kania EM, Oommen OP, Ahmed T, Loaiza S, Parzych K, Dazzi F, Auner HW, Varghese OP, Festy F, Grigoriadis AE, Snijders AP, Bozec L, Gentleman E (2018) “Bi-directional cell-pericellular matrix interactions direct stem cell fate.” Nature Communications. 9:4049. doi: 10.1038/s41467-018-06183-4
Ferreira SA, Faull PA, Seymour A, Yu TTL, Loaiza S, Auner HW, Snijders AP, Gentleman E (2018) “Neighboring cells override 3D hydrogel matrix cues to drive human MSC quiescence.” Biomaterials. 176:13-23. doi: 10.1016/j.biomaterials.2018.05.032
Foyt DA‡, Norman MDA‡, Yu TTL‡, Gentleman E (2018) “Exploiting Advanced Hydrogel Technologies to Address Key Challenges in Regenerative Medicine.” Advanced Healthcare Materials. 1700939. doi: 10.1002/adhm.201700939. ‡equal contribution
Stagg AJ. Intestinal Dendritic Cells in Health and Gut Inflammation. Frontiers in Immunology. 2018 Dec 6;9:2883. doi: 10.3389/fimmu.2018.02883.
Giles EM, Sanders TJ, McCarthy NE, Lung J, Pathak M, MacDonald TT, Lindsay JO, Stagg AJ. Regulation of human intestinal T-cell responses by type 1 interferon-STAT1 signaling is disrupted in inflammatory bowel disease. Mucosal Immunology. 2017 Jan;10(1):184-193. doi: 10.1038/mi.2016.44