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EC GNG metabolism

Endothelial Gluconeogenesis: a novel target for tumor anti-angiogenesis?

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EC-Contrib. €

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Project "EC GNG metabolism" data sheet

The following table provides information about the project.

Coordinator
VIB VZW 

Organization address
address: RIJVISSCHESTRAAT 120
city: ZWIJNAARDE - GENT
postcode: 9052
website: www.vib.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]
 Project website https://www.vibcancer.be/peter-carmeliet
 Total cost 172˙800 €
 EC max contribution 172˙800 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2015
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2017
 Duration (year-month-day) from 2017-01-01   to  2019-02-13

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    VIB VZW BE (ZWIJNAARDE - GENT) coordinator 172˙800.00

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 Project objective

Angiogenesis promotes tumor progression and metastasis; unfortunately current anti-angiogenic strategies targeting endothelial growth factors suffer from limited efficacy and toxicity. The host laboratory pioneered the novel concept that blood vessel forming endothelial cells (ECs) reprogram their metabolism to become glucose-addicted and rely on glycolysis to generate ATP required for angiogenesis. Furthermore, to increase biomass production and maintain redox homeostasis, ECs shunt glycolytic intermediates into glycolysis side-pathways. Further ECs diverge from pre-existing blood vessel into avascular tissue, the scarcer external glucose levels will become. Currently, how ECs maintain the generation of glycolytic intermediates under such conditions remains unknown. One possibility is the de-novo synthesis of these intermediates through gluconeogenesis (GNG).

To date, nothing is known about GNG metabolism in ECs, which underscores the novelty of my proposal. GNG is particularly interesting since preliminary findings indicate that ECs express all enzymes involved in GNG, and impairing this pathway decreases EC proliferation and sprouting. Therefore, through a multi-angled approach, I will unravel the role of GNG in ECs and uncover its contribution to blood vessel sprouting both in normal and pathological angiogenesis.

Ultimately this project will explore whether blocking GNG may inhibit pathological angiogenesis (e.g. cancer) and translate my findings into therapeutic strategies.

 Publications

year authors and title journal last update
List of publications.
2018 Guy Eelen, Pauline de Zeeuw, Lucas Treps, Ulrike Harjes, Brian W. Wong, Peter Carmeliet
Endothelial Cell Metabolism
published pages: 3-58, ISSN: 0031-9333, DOI: 10.1152/physrev.00001.2017
Physiological Reviews 98/1 2019-08-08
2018 Joanna Kalucka, Laura Bierhansl, Nadine Vasconcelos Conchinha, Rindert Missiaen, Ilaria Elia, Ulrike Brüning, Samantha Scheinok, Lucas Treps, Anna Rita Cantelmo, Charlotte Dubois, Pauline de Zeeuw, Jermaine Goveia, Annalisa Zecchin, Federico Taverna, Francisco Morales-Rodriguez, Aleksandra Brajic, Lena-Christin Conradi, Sandra Schoors, Ulrike Harjes, Kim Vriens, Gregor-Alexander Pilz, Rongyuan Chen, Richard Cubbon, Bernard Thienpont, Bert Cruys, Brian W. Wong, Bart Ghesquière, Mieke Dewerchin, Katrien De Bock, Xavier Sagaert, Sebastian Jessberger, Elizabeth A.V. Jones, Bernard Gallez, Diether Lambrechts, Massimiliano Mazzone, Guy Eelen, Xuri Li, Sarah-Maria Fendt, Peter Carmeliet
Quiescent Endothelial Cells Upregulate Fatty Acid β-Oxidation for Vasculoprotection via Redox Homeostasis
published pages: 881-894.e13, ISSN: 1550-4131, DOI: 10.1016/j.cmet.2018.07.016
Cell Metabolism 28/6 2019-08-08
2018 Shawez Khan, Federico Taverna, Katerina Rohlenova, Lucas Treps, Vincent Geldhof, Laura de Rooij, Liliana Sokol, Andreas Pircher, Lena-Christin Conradi, Joanna Kalucka, Luc Schoonjans, Guy Eelen, Mieke Dewerchin, Tobias Karakach, Xuri Li, Jermaine Goveia, Peter Carmeliet
EndoDB: a database of endothelial cell transcriptomics data
published pages: D736-D744, ISSN: 0305-1048, DOI: 10.1093/nar/gky997
Nucleic Acids Research 47/D1 2019-08-08
2017 Brian W Wong, Elke Marsch, Lucas Treps, Myriam Baes, Peter Carmeliet
Endothelial cell metabolism in health and disease: impact of hypoxia
published pages: 2187-2203, ISSN: 0261-4189, DOI: 10.15252/embj.201696150
The EMBO Journal 36/15 2019-08-08
2018 Lucas Treps
EnLIGHTenment of tumor vessel normalization and immunotherapy in glioblastoma
published pages: 3-6, ISSN: 0022-3417, DOI: 10.1002/path.5103
The Journal of Pathology 246/1 2019-08-08

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