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Angiogenesis and HBP

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Glycosylation of angiogenic factors by the hexosamine biosynthetic pathway HBP...

Glycosylation of angiogenic factors by the hexosamine biosynthetic pathway HBP a nutrient sensor with a novel metabolic signaling role in angiogenesis? Angiogenesis, the growth of new blood vessels, is vital for tumour malignancy. Attempts to inhibit it by blocking VEGF has had limited success in the clinic with many patients innately resistant or acquiring resistance over time.... ver más

30/04/2014

VLAAMS INSTITUUT...

177K€

Presupuesto del proyecto: 177K€

Líder del proyecto

VIB VZW No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo FP7 notifico la concesión del proyecto el día 2014-04-30 No tenemos la información de la convocatoria

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1 Participantes

VLAAMS INSTITUUT BIOTECHNOL...

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Líder del proyecto

VIB VZW No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 177K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto Angiogenesis, the growth of new blood vessels, is vital for tumour malignancy. Attempts to inhibit it by blocking VEGF has had limited success in the clinic with many patients innately resistant or acquiring resistance over time. Therefore, novel anti-angiogenic therapeutic strategies are required to improve overall efficacy and reduce resistance. Novel work in the Carmeliet lab has highlighted the importance of the metabolic pathway in regulating the switch from a quiescent endothelial cell to a proliferative one. Little is known about how this angiogenic switch is regulated by metabolism and which metabolic pathways are even involved. One such pathway, the hexoasmine biosynthetic pathway (HBP) generates UDP-GlcNAc, necessary for post-translational modification of proteins via glycosylation. N-linked glycosylation can regulate growth factor receptor exposure on the surface and signaling, while O-linked glycosylation can rapidly alter the function and activity of nuclear and cytosolic proteins, alike phosphorylation. Despite the important roles these modifications have, minimal research has been done into the role of glycosylation in angiogenesis. The proposal of this project is to investigate whether the HBP regulates angiogenesis via a specific glycosylation switch. In particular, using multi-disciplinary gene-discovery, pharmacological and genetic approaches in various animal models (zebrafish; mouse), I propose to investigate whether changes in nutrient supply regulate EC responses (quiescence versus proliferation) through selective HBP-mediated glycosylation of Flk1 or Notch and p53, and to explore the role and relevance of the HBP and key glycosylation pathways in EC quiescence / proliferation in vitro and (pathological) angiogenesis in vivo. The combination of genetic and translational studies might also open novel avenues to develop novel anti-angiogenic therapeutic strategies.

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