Hjalte List Larsen

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My research focuses on understanding mechanisms governing cell state transitions during intestinal development and disease. Using 3D organoid models, we characterize the emergence of intestinal stem cells during development and unravel the transcriptional and epigenetic regulators facilitating progressive maturation in the intestinal epithelium during development. We capitalize on these insights in research focusing on regeneration of the adult intestinal epithelium following injury, as we and others have demonstrated that the adult epithelium is transiently reprogrammed to a fetal-like state during repair of the wounded epithelium. We model in vivo relevant cell state transitions during injury and repair using adult intestinal organoids, and utilize these to uncover novel regulators of fetal-like reprogramming and regeneration in the adult epithelium. By combining organoid cultures with next generation sequencing, single-cell RNA-seq, CRISPR-Cas9 based gene editing, proteomics and functional assays in vitro and in vivo, we ultimately aim at developing conceptually novel treatment strategies to enhance endogenous epithelial regeneration in patients suffering from inflammatory bowel disease.