Differential phosphorylation of CXCR4 and CXCR7

Early stage researcher 10 (ESR10) project – Aurelien Zarca
Supervision: Prof MJ Smit, Dr M Siderius, Dr H Vischer, Prof R Leurs
Host: VU (NL) – VU University Amsterdam, Dept. of Medicinal Chemistry

I- Project proposal:

1. Delineate ligand (in)dependent CXCR4 and CXCR7 phosphorylation profiles.

2. Determine kinases involved in CXCR4 and CXCR7 phosphorylation.

3. Define functional consequences of differential CXCR4 and CXCR7 phosphorylation in distinct cancer cell types.

To study the role of CXCR4 and CXCR7 phosphorylation, receptor mutants and phosphospecific antibodies will be used and/or generated. To identify the kinases involved FRET/BRET and gene silencing experiments will be performed. The functional consequences of differential phosphorylation in various cancer cell lines will be explored by focussing on receptor desensitization/trafficking using confocal fluorescence microscopy and automated high content screening and signalling to multiple intracellular pathways (bias).

Planned secondments: arGEN-X (BE), UWUE (DE), Vivia Biosystems (ES)


II- Requirement candidate:

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

Required expertise: cell culture, cell-based assays, biochemistry, molecular biology. Recommended expertise: GPCR molecular pharmacology, chemokine biology, imaging, FRET/BRET based signalling, radioligand binding, oncogenic assays.

Key publications:
1. Maussang D, et al, Smit MJ (2013) Llama-derived single variable domains (Nanobodies) directed against CXCR7 reduce head and neck cancer cell growth in vivo. J Biol Chem 288: 29562-72.

2. Canals M, Scholten DJ, de Munnik S, Han MK, Smit MJ, Leurs R (2012) Ubiquitination of CXCR7 controls receptor trafficking. PLoS One. 7:e34192.

3. Watts AO, Verkaar F, van der Lee MM, Timmerman CA, Kuijer M, van Offenbeek J, van Lith LH, Smit MJ, Leurs R, Zaman GJ, Vischer HF (2013) β-Arrestin recruitment and G protein signaling by the atypical human chemokine decoy receptor CCX-CKR. J Biol Chem 288:7169-81.

4. Jähnichen S et al Smit MJ (2010) CXCR4 nanobodies (VHH-based single variable domains) potently inhibit chemotaxis and HIV-1 replication and mobilize stem cells. Proc Natl Acad Sci USA. 107: 20565.

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Great way to finish the week off with some #FCS measurements of CXCR4-expressing HEK cells at @UoNLifeSci 🔬 #FluorescenceFriday

Hello everyone!
I am Noemi Karsai and I’m the next in our #ESR introduction series. I’m #ESR11 and I’m originally from Hungary, currently doing my PhD at @UoNLifeSci @COMPARE_UoBUoN, UK.

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Hello 🙂
I am here to continue the series in which all #ESRs are presenting themselves. I am Viviana Marolda and I am in my first year of PhD. I am #ESR13, originally from Italy, and currently, I am working as a PhD student in @CBMSO_CSIC_UAM, at Universidad Autonoma de Madrid.

Hey twitter!
I am @DehanComez. I am taking over the Oncornet account for a while to start a series of all #ESRs writing about themselves and their projects. I am #ESR5, originally from Turkey and right now I am working as a PhD student in @COMPARE_UoBUoN , @UniofNottingham , UK.

New review on #gpcr structural dynamics out in COSB. Great teamwork with the @JanaSelent group. Thanks to @Lundbeckfonden and @novonordiskfond https://lnkd.in/eyjrA5V

ONCORNET2.0 is the successor to #ONCORNET. You can see some of the work of ESRs from the first ONCORNET in this special issue of @MolPharmJournal from 2019, with reviews on #CXCR4 and #ACKR3 structure and function: https://molpharm.aspetjournals.org/content/96/6

Hi everyone – we’re on Twitter! ONCORNET2.0 is a #MarieCurie ITN of 16 ESRs across Europe studying #chemokine #GPCRs #CXCR4 and #ACKR3 in cancer. Our projects cover molecular dynamics, medchem, #pharmacology through to translational work. Follow us for updates from our ESRs!

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Contact details

Please contact us at:

ONCORNET Coordinator
VU University Amsterdam
The Netherlands