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Master thesis: Study of the Yap-Hippo and Wnt Pathways for Intestinal Regeneration in an Ex Vivo Small Intestinal 3D Organoid Model. Hochschule Mannheim.

Ruffner, Heinz (2013) Master thesis: Study of the Yap-Hippo and Wnt Pathways for Intestinal Regeneration in an Ex Vivo Small Intestinal 3D Organoid Model. Hochschule Mannheim. Master thesis, not published, presented to supervisor at Hochschule Mannheim under CDA..

Abstract

Tissue regeneration plays a crucial role in epithelial wound healing, such as the intestinal epithelium following cancer therapy. Cancer patients often suffer from very painful mucositis in the oral cavity and the intestine in response to radiation therapy. Epithelial regeneration is driven by stem cells, and this process is impaired in following radiation. The Wnt pathway constitutes a key player of stem cell activity, and interaction of Wnt and Yap signaling pathways are thought to act in a sensitive balance during epithelial wound healing. However, the molecular interactions and roles of both pathways during intestinal regeneration are still not clear. In the present study the impact of Yap pathway on the stem cell proliferation controlling Wnt signaling was investigated. Three dimensional ex vivo models of murine small intestinal organoids were used to investigate stem cells in their physiological environment. The effect of Yap absence on Wnt signaling was studied by deletion of Yap in organoids. To do so, transient transfection methods like lipofection and electroporation needed first to be established for the primary multicellular organoids. Since these transient transfection methods showed sub-optimal efficiency, an approach to inducible delete Yap via adeno associated virus- and adenovirus-mediated gene transfer was applied. Results of this project provided no evidence of direct Yap pathway influence on Wnt target gene expression.

Item Type: Article
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Additional Information: Master thesis, not published, presented to supervisor at Hochschule Mannheim under CDA.
Keywords: Master thesis.
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Date Deposited: 13 Oct 2015 13:13
Last Modified: 13 Oct 2015 13:13
URI: https://oak.novartis.com/id/eprint/11375

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