Description du projet
Étudier les mécanismes du cancer lié au virus d’Epstein-Barr
Le virus d’Epstein Barr (VEB) est à l’origine d’environ 200 000 nouveaux cas de cancer chaque année. Une manière potentiellement efficace de traiter les personnes atteintes de cancer lié au VEB consiste à utiliser des inhibiteurs de petites molécules ciblant des protéines virales. Toutefois, ce type de médicaments n’existe pas. De récentes données scientifiques indiquent que le BILF1 codé par le VEB, un récepteur couplé aux protéines G constitutivement actif, pourrait faire avancer le développement de médicaments antiviraux pour traiter les tumeurs liées au VEB. Le projet VirGO, financé par l’UE, entend explorer le rôle du BILF1 dans la transformation des lymphocytes B du centre germinatif et déterminer la manière dont le BILF1 contribue à l’établissement du phénotype des cellules de lymphome de Burkitt. Il fera également le lien entre ces phénotypes et les caractéristiques pathologiques des tumeurs primitives, et la réponse des patients au traitement. Le projet permettra de mieux comprendre les mécanismes d’oncogenèse induits par le VEB.
Objectif
The Epstein–Barr virus (EBV) is widespread in all human communities. While most people carry EBV as a life-long asymptomatic infection, in some people, EBV contributes to malignant transformation and is responsible for ~200,000 new cancer cases/year. Small molecule inhibitors targeting viral proteins could be an effective option to treat people with EBV-associated cancers. However, no such drugs exists which in part reflects the limited repertoire of targetable virus proteins present in EBV-driven cancers. Recently, the Experienced Researcher (ER) has shown that the tumour cells of EBV-associated cancers such as Burkitt lymphoma (BL), express the EBV-encoded BILF1, a constitutively active G-protein coupled receptor (GPCR). Furthermore, preliminary data by the ER indicate that BILF1 partially recapitulates the aberrant transcriptional programme of BL and is likely to do so through activation of oncogenic cell signalling pathways that include AKT-mTOR. These data suggest that BILF1 could be a realistic therapeutic target, raising the possibility of advancing the development of anti-viral drugs to treat EBV-related tumours; GPCRs are the most successful class of drug target for the treatment of human disorders and are emerging as anti-cancer targets. In this project the ER will harness new models of B cell lymphomagenesis available in the host laboratory to: 1) Explore the role of BILF1in the transformation of germinal centre B cells; the progenitors of BL; 2) Identify how BILF1 contributes to the established phenotype of BL cells; and 3) Link these phenotypes to pathological features of the primary tumour and to patient response to therapy. Thus, the Fellowship will significantly advance knowledge of the mechanisms of EBV-mediated oncogenesis, in turn paving the way for the development of new EBV-targeted small molecule drugs. The ER will emerge from this project with a new advanced skill-set and the capability to launch her own high level scientific research.
Champ scientifique
- natural sciencesbiological sciencescell biologycell signaling
- natural sciencesbiological sciencesmicrobiologyvirology
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- medical and health sciencesclinical medicineoncology
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantivirals
Mots‑clés
Programme(s)
Régime de financement
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinateur
- Limerick
Irlande