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Neogenesis of new functional Beta Cells through Modulation of Neurogenin-3 Expression to provide Regenerative Therapy for Diabetes Patients

Objective

Diabetes mellitus is a chronic metabolic disorder characterized by elevated blood sugar levels with increased risk of cardiovascular complications. The currently available therapy for type 1 diabetes (TIDM) consists of daily injections of exogenous insulin in order to delay disease progression. However, these treatments do not provide a real cure since long-term secondary complications cannot be avoided. As TIDM is characterized by the highly specific immune-mediated destruction of one cell type, this disease represents a particularly ideal candidate for cell replacement therapy. Transplantation of human islets, isolated from cadaveric donor pancreas, potentially represents a genuine cure for TIDM but is limited by a shortage of transplantable islets.
In the current application I will create an unprecedented humanized mouse model to test pharmacological therapies for diabetes. In a first step I will study the actions of Geminin on the regulation of the pro-endocrine transcription factor Neurogenin3 during mouse and human development and postnatal beta cell regeneration from the exocrine cells of the pancreas. These experiments will provide tools to control Neurogenin3 expression and thus endocrine cell differentiation in the human pancreas. Using the knowledge gained from in vivo mouse studies, I will create a novel clinically relevant humanized mouse model. I will use this model to develop a cytokine-based treatment to convert human acinar cells to functional beta-like cells in a Neurogenin3 dependent way. Finally, I will design a strategy to deliver the pro-endocrine treatment in a cell-specific manner. The humanized model will serve as a unique platform to test treatment for human diabetes in the pre-clinical phase.
This project utilizes a multidisciplinary approach to develop a strategy based on pharmacological treatment rather than cell therapy, paving the way for clinical application.

Fields of science (EuroSciVoc)

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Topic(s)

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Funding Scheme

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ERC-STG - Starting Grant

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Call for proposal

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(opens in new window) ERC-2015-STG

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Host institution

VRIJE UNIVERSITEIT BRUSSEL
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.

€ 1 499 875,00
Address
PLEINLAAN 2
1050 Bruxelles / Brussel
Belgium

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Region
Région de Bruxelles-Capitale/Brussels Hoofdstedelijk Gewest Région de Bruxelles-Capitale/ Brussels Hoofdstedelijk Gewest Arr. de Bruxelles-Capitale/Arr. Brussel-Hoofdstad
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.

€ 1 499 875,00

Beneficiaries (1)

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