Mara Cirone
Laureata in Medicina e Chirurgia, dottorata in Medicina Sperimentale e specializzata in Allergologia e Immunologia Clinica. È impegnata da diversi anni sulla ricerca riguardanti i virus in grado di causare tumori (oncogeni).
“Il progetto appena finanziato si focalizza sui gammaherpesvirus (EBV e KSHV). Il virus di Epstein-Barr (EBV) causa diverse malattie, tra cui la mononucleosi e può dar vita a diversi tipi di tumore, tra cui il carcinoma rinofaringeo. Nuovi studi condotti a livello mondiale hanno inoltre rivelato il ruolo centrale di EBV nel 5-10% dei carcinomi gastrici. Il KSHV (Kaposi sarcoma associated herpes virus) è invece causa del sarcoma di Kaposi – tumore che prende origine dalle cellule che ricoprono l’interno dei vasi sanguigni o linfatici e può manifestarsi a livello di cute, mucose e organi interni. Con questa ricerca si intende studiare come questi virus manipolano, a loro favore, i normali processi cellulari. Lo scopo è di individuare molecole bersaglio da utilizzare per contrastare la tumorigenesi mediata da questi virus”.
Autophagy manipulation as a strategy to counteract EBV- and KSHV-driven malignancies.
The object of this study was to evaluate whether autophagy dysregulation could be involved in the malignant transformation induced by EBV and KSHV, two gammaherpesviruses strongly associated to human cancer. Autophagy plays an important role in the different phases of cancerogenesis, including cancer onset, progression and response to therapies. Both viruses encode for several proteins that directly or indirectly impair autophagy and accordingly, we have previously shown that they promote the first steps of autophagy while block the final steps to optimize their replication. Interestingly, autophagy inhibition has been reported to contribute to the malignant transformation, leading to misfolded protein and ROS accumulation. Our recent findings show that EBV activated STAT3, reduced autophagy and increased ROS level in infected B cells to promote their transformation into LCLs, as indicated by the use of quercetin that by reducing such effects, prevented EBV-driven transformation. Studies are in progress to evaluate the involvement of autophagy in KSHV-mediated transformation and whether the rescue of autophagy could interfere with it.
