DISRUPTION OF E-CADHERIN PROMOTES INTESTINAL STEM CELL PROLIFERATION IN COLONOIDS

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dc.contributor.advisorJin, Younggeon
dc.contributor.authorArpon, Aaliyah
dc.contributor.authorBell, Michaela
dc.contributor.authorBrown, Katie
dc.contributor.authorForsberg, Alisa
dc.contributor.authorKrishnan, Ananya
dc.contributor.authorMargolis, Ryan
dc.contributor.authorMarhefka, Laura
dc.contributor.authorYang, Jerry
dc.contributor.authorYardi, Isha
dc.date.accessioned2024-03-12T15:41:13Z
dc.date.available2024-03-12T15:41:13Z
dc.date.issued2023
dc.description.abstractReconstitution of the wounded epithelium is integral to achieve the full healing of the gut mucosa in treating Inflammatory Bowel Disease (IBD). The ability of intestinal stem cells (ISCs) to indefinitely self-renew while generating new functional epithelia makes them a potential therapeutic tool for IBD. Transmembrane protein E-cadherin, a calcium dependent cell-to-cell adhesion protein at adherens junctions, also regulates the Wnt signaling pathway. The canonical Wnt (β-catenin dependent) pathway is vital for the ISC homeostasis and regeneration. However, the role of E-cadherin in ISCs is an important yet notably understudied phenomenon. Disruption of E-cadherin increases unbound cytosolic β-catenin levels, which go to the nucleus and increase transcription of Wnt target genes. We hypothesize that disrupted E-cadherin will increase proliferation of ISCs. In our experiments, we disrupt E-cadherin with different concentrations of EGTA, a calcium chelator, and see the effect it has on colonoid growth and development. Our experiments showed that with EGTA there was greater proliferation; 1 mM EGTA experimental groups had larger colonoids than vehicle control colonoids on day 6 after seeding. This indicates that EGTA treatment may induce proliferation of the organoid with E-cadherin disruption. For future study, we will check and confirm the disruption of E-cadherin/β-catenin complex and Wnt target genes by real-time PCR and immunofluorescence studies. Ultimately our study will open novel therapeutic applications for patients living with IBD and other clinic inflammatory gut disorders.
dc.identifierhttps://doi.org/10.13016/zzpr-wzrp
dc.identifier.urihttp://hdl.handle.net/1903/32363
dc.relation.isAvailableAtDigital Repository at the University of Maryland
dc.relation.isAvailableAtGemstone Program, University of Maryland (College Park, Md)
dc.subjectGemstone Team MINIGUT
dc.titleDISRUPTION OF E-CADHERIN PROMOTES INTESTINAL STEM CELL PROLIFERATION IN COLONOIDS
dc.typeThesis
local.equitableAccessSubmissionNo

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