Maria G. Masucci's Group
Molecular Mechanisms of Viral Oncogenesis
The co-evolution of viruses with their hosts has led to the selection of a broad repertoire of viral strategies for manipulation of the cellular environment. By acting as a Trojan horse for cell invasion, viruses have taught us many of the basic principles that regulate cell proliferation, differentiation and death. Our research focuses on human tumor viruses.
Papilloma viruses (HPV), hepatitis B- (HBV) and C-viruses (HCV), Epstein-Barr virus (EBV), Kaposi sarcoma virus (KSHV), human T-cell-leukemia virus (HTLV) may contribute to the pathogenesis of as much as 15-20% of all human cancers. A common feature of these oncogenic viruses is their capacity to establish persistent infections that are either asymptomatic or are accompanied by benign cell proliferations. Progression to malignancy is associated with the expression of viral proteins whose primary function is to drive virus replication by regulating cell proliferation, apoptosis and the recognition of infected cells by the immune system. Many of these viral products interfere with the ubiquitin-proteasome system (UPS) that controls protein turnover and trafficking.
Our main virus model is EBV, a lymphotropic herpes virus that is associated with lymphoid and epithelial cell malignancies including Burkitt's lymphoma (BL), nasopharyngeal carcinoma (NPC), immunoblastic lymphoma (IL) and Hodgkin's disease (HD). We study the mechanism by which EBV proteins expressed in malignant cells modify the cellular environment and regulate the interaction of the infected cells with the host immune system.
|Javier Avila||Senior researcher|
Herpes virus deneddylases interrupt the cullin-RING ligase neddylation cycle by inhibiting the binding of CAND1.
J Mol Cell Biol 2012 Aug;4(4):242-51
The Epstein-Barr virus nuclear antigen-1 promotes telomere dysfunction via induction of oxidative stress.
Leukemia 2011 Jun;25(6):1017-25
A deneddylase encoded by Epstein-Barr virus promotes viral DNA replication by regulating the activity of cullin-RING ligases.
Nat. Cell Biol. 2010 Apr;12(4):351-61
Three Epstein-Barr virus latency proteins independently promote genomic instability by inducing DNA damage, inhibiting DNA repair and inactivating cell cycle checkpoints.
Oncogene 2009 Nov;28(45):3997-4008
Epstein-Barr virus promotes genomic instability in Burkitt's lymphoma.
Oncogene 2007 Aug;26(35):5115-23