Periodic Reporting for period 1 - VirGO (VIRGO: Studying a VIRal Gpcr in Oncogenesis)
Periodo di rendicontazione: 2020-09-14 al 2022-09-13
The Epstein-Barr virus (EBV) is a herpesvirus which infects more than 90% of people worldwide. While in the majority of cases the virus induces an asymptomatic infection, in a small percentage of persons, the virus contributes to malignant transformation, causing at least nine types of cancer, including Burkitt lymphoma (BL), one of the most important EBV-associated paediatric tumours. Totally, EBV accounts for 200,000 new cancer cases and over 142,000 deaths worldwide every year. However, deaths from EBV-associated cancers have increased by 14.6% since 1990 and are predicted to increase further.
Although EBV is a problem of worldwide importance, no vaccine or antiviral drug has yet been approved, in part due to the limited number of targetable virus proteins present in EBV-driven cancers. Recent scientific data suggest that the tumour cells of EBV-associated cancers such as BL express the EBV-encoded BILF1, a constitutively active G-protein coupled receptor (GPCR). GPCRs are currently the most effective class of pharmacological targets for the treatment of human conditions, and they are also becoming important anti-cancer targets. EBV-encoded BILF1 shows many similarities with other viral GPCRs and might be a realistic therapeutic target for EBV-associated malignancies. However, its function is largely unknown.
This European Fellowship has allowed a young researcher of proven ability to investigate the role of BILF1 in lymphomagenesis in an internationally renowned laboratory. Specifically, the EU-funded VirGO project aimed to: (i) explore the role of BILF1 in EBV-negative germinal centre B-cell (GC-B) transformation, the progenitor of BL; (ii) identify how BILF1 contributes to the established phenotype of BL cells; (iii) and link these phenotypes to BL primary tumour pathological features and to patient response to therapy.
Although EBV is a problem of worldwide importance, no vaccine or antiviral drug has yet been approved, in part due to the limited number of targetable virus proteins present in EBV-driven cancers. Recent scientific data suggest that the tumour cells of EBV-associated cancers such as BL express the EBV-encoded BILF1, a constitutively active G-protein coupled receptor (GPCR). GPCRs are currently the most effective class of pharmacological targets for the treatment of human conditions, and they are also becoming important anti-cancer targets. EBV-encoded BILF1 shows many similarities with other viral GPCRs and might be a realistic therapeutic target for EBV-associated malignancies. However, its function is largely unknown.
This European Fellowship has allowed a young researcher of proven ability to investigate the role of BILF1 in lymphomagenesis in an internationally renowned laboratory. Specifically, the EU-funded VirGO project aimed to: (i) explore the role of BILF1 in EBV-negative germinal centre B-cell (GC-B) transformation, the progenitor of BL; (ii) identify how BILF1 contributes to the established phenotype of BL cells; (iii) and link these phenotypes to BL primary tumour pathological features and to patient response to therapy.
The research project was conducted via three main work packages (WPs) which led to:
(a) attending seven international conferences as: member of the organising committee (1); moderator (1); speaker or invited speaker (5);
(b) five peer-reviewed articles;
and additional three conferences as invited speaker, and four manuscripts underway.
The project also contained an additional WP which involved management, training, and knowledge transfer. In it, the Fellow attended intensive training workshops and multi-day conferences, being able to learn and develop a number of skills important for career development and skill transfer. These included: improving her grasp of the English language; advancing her interest and skills in advanced molecular techniques; teaching undergraduates; mentoring PhD students and early career researchers; presenting and sharing her work with her peers. Via this MSCA grant, the Fellow has also provided leadership in publishing by serving as: (1) Guest Editor in several Special Issues (Cancers; Frontiers in Immunology; Life Journal); (2) Member of Editorial Board for Artificial Intelligence in Cancer; (3) Member of Topical Advisory Panel for Cancers Journal; (4) Peer reviewer for academic journals (i.e Frontiers, Scientific report, BMC) in the EBV field; (5) Corresponding and last author in two peer-reviewed articles; (6) Author of an Issue Book.
(a) attending seven international conferences as: member of the organising committee (1); moderator (1); speaker or invited speaker (5);
(b) five peer-reviewed articles;
and additional three conferences as invited speaker, and four manuscripts underway.
The project also contained an additional WP which involved management, training, and knowledge transfer. In it, the Fellow attended intensive training workshops and multi-day conferences, being able to learn and develop a number of skills important for career development and skill transfer. These included: improving her grasp of the English language; advancing her interest and skills in advanced molecular techniques; teaching undergraduates; mentoring PhD students and early career researchers; presenting and sharing her work with her peers. Via this MSCA grant, the Fellow has also provided leadership in publishing by serving as: (1) Guest Editor in several Special Issues (Cancers; Frontiers in Immunology; Life Journal); (2) Member of Editorial Board for Artificial Intelligence in Cancer; (3) Member of Topical Advisory Panel for Cancers Journal; (4) Peer reviewer for academic journals (i.e Frontiers, Scientific report, BMC) in the EBV field; (5) Corresponding and last author in two peer-reviewed articles; (6) Author of an Issue Book.
The results of this MSCA are reported in 4 forthcoming papers. The research performed significantly advanced knowledge of the mechanisms of EBV-mediated oncogenesis, highlighting a crucial role of BILF1 in B-cell transformation and in BL pathogenesis. Moreover, these findings provide a strong experimental basis and scientific rationale for the progression of an anti-BILF1-based therapy for EBV-associated malignancies. These are extremely interesting results in light of the fact that no vaccine or antiviral drug against EBV has yet been approved. Also, the knowledge gained about how BILF1 induces either B-cell transformation or BL may be applicable to other EBV-associated malignancies, thus providing a platform from which we will be able to better decipher and therapeutically address aspects of diseases related to EBV.
Impacts anticipated from the MSCA are increased and improved: new findings on how BILF1 induces B-cell transformation have been made; new acknowledgments on the role of EBV in the pathogenesis of B-lymphomas have been provided; new avenues of research have been opened; new market opportunities have been created; new ways to develop new EBV-targeted small molecule drugs with important benefits for society have been paved. Many manuscripts that are currently under development using data collected during this fellowship will continue to have a great impact in the coming years. In the end, the data generated thus far will form the core of several scientific publications that the research community will be able to build on.
Impacts anticipated from the MSCA are increased and improved: new findings on how BILF1 induces B-cell transformation have been made; new acknowledgments on the role of EBV in the pathogenesis of B-lymphomas have been provided; new avenues of research have been opened; new market opportunities have been created; new ways to develop new EBV-targeted small molecule drugs with important benefits for society have been paved. Many manuscripts that are currently under development using data collected during this fellowship will continue to have a great impact in the coming years. In the end, the data generated thus far will form the core of several scientific publications that the research community will be able to build on.