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Neobetacell SIGNED

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

Total Cost €

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EC-Contrib. €

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Partnership

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Project "Neobetacell" data sheet

The following table provides information about the project.

Coordinator
VRIJE UNIVERSITEIT BRUSSEL 

Organization address
address: PLEINLAAN 2
city: BRUSSEL
postcode: 1050
website: www.vub.ac.be

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Belgium [BE]
 Total cost 1˙499˙875 €
 EC max contribution 1˙499˙875 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2015-STG
 Funding Scheme ERC-STG
 Starting year 2016
 Duration (year-month-day) from 2016-10-01   to  2021-09-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    VRIJE UNIVERSITEIT BRUSSEL BE (BRUSSEL) coordinator 1˙499˙875.00

Map

 Project 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.

 Publications

year authors and title journal last update
List of publications.
2018 Shiue-Cheng Tang, Luc Baeyens, Chia-Ning Shen, Shih-Jung Peng, Hung-Jen Chien, David W. Scheel, Chester E. Chamberlain, Michael S. German
Human pancreatic neuro-insular network in health and fatty infiltration
published pages: 168-181, ISSN: 0012-186X, DOI: 10.1007/s00125-017-4409-x
Diabetologia 61/1 2019-06-06
2018 Andreia V. Pinho, Mathias Van Bulck, Lorraine Chantrill, Mehreen Arshi, Tatyana Sklyarova, David Herrmann, Claire Vennin, David Gallego-Ortega, Amanda Mawson, Marc Giry-Laterriere, Astrid Magenau, Gunther Leuckx, Luc Baeyens, Anthony J. Gill, Phoebe Phillips, Paul Timpson, Andrew V. Biankin, Jianmin Wu, Ilse Rooman
ROBO2 is a stroma suppressor gene in the pancreas and acts via TGF-β signalling
published pages: , ISSN: 2041-1723, DOI: 10.1038/s41467-018-07497-z
Nature Communications 9/1 2019-06-06
2018 Violette Coppens, Gunter Leuckx, Yves Heremans, Willem Staels, Yannick Verdonck, Luc Baeyens, Nico De Leu, Harry Heimberg
Semi-automated digital measurement as the method of choice for beta cell mass analysis
published pages: e0191249, ISSN: 1932-6203, DOI: 10.1371/journal.pone.0191249
PLOS ONE 13/2 2019-06-06
2018 Luc Baeyens, Marie Lemper, Willem Staels, Sofie De Groef, Nico De Leu, Yves Heremans, Michael S. German, Harry Heimberg
(Re)generating Human Beta Cells: Status, Pitfalls, and Perspectives
published pages: 1143-1167, ISSN: 0031-9333, DOI: 10.1152/physrev.00034.2016
Physiological Reviews 98/3 2019-06-06
2018 Willem Staels, Yannick Verdonck, Yves Heremans, Gunter Leuckx, Sofie De Groef, Carlo Heirman, Eelco de Koning, Conny Gysemans, Kris Thielemans, Luc Baeyens, Harry Heimberg, Nico De Leu
Vegf-A mRNA transfection as a novel approach to improve mouse and human islet graft revascularisation
published pages: 1804-1810, ISSN: 0012-186X, DOI: 10.1007/s00125-018-4646-7
Diabetologia 61/8 2019-06-06
2017 Zachary Pappalardo, Deeksha Gambhir Chopra, Thomas G. Hennings, Hunter Richards, Justin Choe, Katherine Yang, Luc Baeyens, Kenny Ang, Steven Chen, Michelle Arkin, Michael S. German, Michael T. McManus, Gregory M. Ku
A Whole-Genome RNA Interference Screen Reveals a Role for Spry2 in Insulin Transcription and the Unfolded Protein Response
published pages: 1703-1712, ISSN: 0012-1797, DOI: 10.2337/db16-0962
Diabetes 66/6 2019-06-06

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