Development of (patho)physiological in vitro and in vivo models to assess effect of CXCR4/CXCR7 modulators

Early stage researcher 13 (ESR13) project – Carmen Callego
Supervision: Prof F Bachelerie, Dr G Schlecht-Louf
Host: INSERM (FR) – UMR S 996, Paris-Sud University, Laboratory of Excellence in Research on Medication and Innovative Therapeutics (LERMIT)

I- Project proposal:

Aim:
1. Investigate the activities of CXCR4/CXCR7 in response to their modulators in cell proliferation/differentiation.

2. Investigate CXCR4-mediated cell migration to characterize partners and the impact of CXCR7.

3. Investigate the effect of CXCR4 and CXCR7 activities on tumour angiogenesis.

Methodology:
The aim is to characterize the role of CXCR4 partners and the impact of CXCR7, in the CXCL12-driven migration (chemotaxis and haptotaxis), proliferation, differentiation and angiogenesis notably in the context of experimental models for oncogenic human papillomavirus (HPV) (e.g. in vitro in wound healing assays and 3D epithelial models and in vivo in mice models; xenograft and transgenic). In these models, partners-expression will be altered via silencing and CRISPR/Cas9 methods and the impact of CXCR4 or CXCR7 mutants as well their modulators will be analysed. Analyses will be extended to biopsies (paired skin/blood samples) from immunodeficient patients suffering from severe HPV pathogenesis (dysplasia, cancer) by mass cytometry [CyTOF permitting multiparametric analyses of rare populations] to validate the oncosignalling pathways.

Planned secondments: Cisbio (FR), VU (NL).

 

II- Requirement candidate:

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

Required expertise:
Biochemistry, molecular biology, cell culture.

Recommended expertise:
HTRF/BRET-based assays, imaging, viral-particle-related assays, Flow-cytometry, mice model practice.

Key publications:
1. Balabanian K, Brotin E, Biajoux V, Bouchet-Delbos L, Lainey E, Fenneteau O, Bonnet D, Fiette L, Emilie D, Bachelerie F (2012) Proper desensitization of CXCR4 is required for lymphocyte development and peripheral compartmentalization in mice. Blood 119:5722-30.

2. Bachelerie F, Graham GJ, Locati M, Mantovani A, Murphy PM, Nibbs R, Rot A, Sozzani S, Thelen M. (2014) New nomenclature for atypical chemokine receptors. Nat Immunol. 2014 15:207-8.

3. Calmette J, Ellouze M, Tran T, Karaki S, Ronin E, Capel F, Pallardy M, Bachelerie F, Krzysiek R, Emilie D, Schlecht-Louf G, Godot V(2014) Glucocorticoid-induced leucine zipper enhanced expression in dendritic cells is sufficient to drive regulatory T cells expansion in vivo. J Immunol. 193:5863-72.

4. Chow KY, Brotin E, Ben Khalifa Y, Carthagena L, Teissier S, Danckaert A, Galzi JL, Arenzana-Seisdedos F, Thierry F, Bachelerie F (2010) A pivotal role for CXCL12 signaling in HPV-mediated transformation of keratinocytes: clues to understanding HPV-pathogenesis in WHIM syndrome. Cell Host & Microbe. 8:523-33.

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My project will be focused on the role of #CXCR4/ACKR3/GRK2 -governed networks in cancer cell migration and metastasis.

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.

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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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Public service announcement: our Marie-Curie ITN @ONCORNET1 is on Twitter! The 16 wonderful #ECRs working on the project will soon be Tweeting about #GPCR #chemokine #ECR life and #pharmacology

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Contact details

Please contact us at:
info@oncornet.eu

ONCORNET Coordinator
VU University Amsterdam
The Netherlands