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Defining the origin of Barrett’s oesophagus by exploring a submucosal gland stem cell model

Objective

Esophageal adenocarcinoma is the most rapidly increasing form of cancer in the Western world characterized by short survival times. Its precursor lesion is Barretts oesophagus, which is present long before oesophageal adenocarcinoma arises. This offers an opportunity for prevention. However, the cell of origin of Barretts oesophagus is unknown. This represents a huge knowledge gap and impairs the development of preventative and curative therapies.

My research has shown homeobox transcription factor HOXA13 is expressed in both Barretts oesophagus and in a fraction of oesophageal submucosal gland cells, but not in differentiated epithelial cells of the oesophagus or stomach. The submucosal glands have been proven to have positional and mutational kinship with Barrett's oesophagus. Therefore, they likely contain its cell of origin. Currently, the only models with oesophageal submucosal gland cells are large laboratory animals. These don't contain human cells, are impractical, costly and unethical in their use. Therefore, I propose to establish and validate the first human, 2D, organoid based, model of these glands.

I propose to test if submucosal glands contain the (HOXA13+) tissue specific stem cell of Barrett's oesophagus by employing single cell culture and single cell visualisation techniques. If proven, the resulting identification of the cell of origin of Barretts oesophagus would open a clear path to understanding mucosal plasticity and early stage oesophageal carcinogenesis. I propose to elucidate the characteristics of this cell of origin and identify which signaling pathways mediate the emergence of Barretts oesophagus. The proposed host group of Prof. Krishnadath is well-positioned for executing this project due to their access to relevant tissues and experience with handling submucosal glands, organoid technology and Barretts oesophagus experimental models. The results and experience gained will be instrumental for my further scientific career.

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Topic(s)

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2022-PF-01

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Coordinator

UNIVERSITEIT ANTWERPEN
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 191 760,00
Address
PRINSSTRAAT 13
2000 Antwerpen
Belgium

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Region
Vlaams Gewest Prov. Antwerpen Arr. Antwerpen
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

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