Role of G protein-coupled receptor kinases (GRKs) in CXCR4 and CXCR7 signalling and modulation

Early stage researcher 8 (ESR8) project – Maria Martins Neves
Supervision: Prof F Mayor, Dr P Penela, Dr C Murga
Host: UAM (ES) – Universidad Autónoma de Madrid, Department of Molecular Biology, Center for Molecular Biology “Severo Ochoa”

I- Project proposal:

1. Identify the GRK subtypes engaged by CXCR4/CXCR7 modulators in healthy and cancer cells.

2. Analyse the effect of altered GRK subtype levels on CXCR4 and CXCR7-mediated signalling and in vivo angiogenesis and cancer progression.

Cell signalling techniques, Co-ip and confocal microscopy in cell models with different GRK dosage, 2D and 3D migration/invasion assays, XCell-based adhesion and proliferation assays, in vivo angiogenesis and xenografts in already available mice models (GRK2 hemizygous, endothelial-specific GRK2 KO, inducible GRK2 KO).

Planned secondments: UWUE (DE), VU (NL).


II- Requirement candidate:

Required diploma: MSc degree in molecular/biomedical Life Sciences, Pharmaceutical Sciences or related Life Sciences degree.

Required expertise: cell culture, cell-based assays, biochemistry, molecular biology. Recommended expertise: GPCR signalling, confocal microscopy, migration and proliferation assays, in vivo murine cancer models

Key publications:
1. Rivas V, Carmona R, Muñoz-Chápuli R, Mendiola M, Nogués L, Reglero C, Miguel-Martín M, García-Escudero R, Dorn GW 2nd, Hardisson D, Mayor F Jr*, Penela P* (*, corresponding authors) (2013) Developmental and tumoral vascularization is regulated by G protein-coupled receptor kinase 2. J Clin Invest. 123:4714-30.

2. P. Penela, L. Nogués and F. Mayor jr (2014) Role of G protein-coupled receptor kinases in cell migration. Current Opinion in Cell Biology 27. 10-17.

3. Avendaño MS, Lucas E, Jurado-Pueyo M, Martínez-Revelles S, Vila-Bedmar R, Mayor F Jr, Salaices M, Briones AM, Murga C (2014) Increased Nitric Oxide Bioavailability in Adult GRK2 Hemizygous Mice Protects Against Angiotensin II-Induced Hypertension. Hypertension 63:369-75.

4. Lafarga, V., Aymerich, I., Tapia, O., Mayor, F. Jr.* & Penela, P* (*, corresponding authors) (2012) A novel GRK2/HDAC6 interaction modulates cell spreading and motility”. EMBO J.

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