James C. Romero-Masters
Position title: Kenney Laboratory
M7503 Wi Institute Medical Research
1111 Highland Ave
Madison, WI 53705
Research Title. Roles of EBV latency genes EBNA3A and EBNA3C in vivo using a cord-blood humanized mouse model
Research Description. Epstein-Barr Virus (EBV) is a DNA tumor virus that infects >90% of the world’s population. EBV is the main causative agent of infectious mononucleosis and is a DNA tumor virus that is associated with B-cell and epithelial-cell malignancies. EBV is able to transform primary B-cells in vitro and encodes 5 genes that are required for B-cell transformation in vitro. Our lab has previously shown that LMP1, which is absolutely required for in vitro transformation of B-cells, is not essential for tumorigenesis in vitro using a cord blood-humanized mouse model (Ma et al. 2015 JCI), because human CD4 T-cells substitute for CD40 ligand-like effect of LMP1. The EBV EBNA3A and EBNA3C genes are also required for B-cell transformation in vitro, because they down-regulate the tumor suppressor genes, p14ARF and p16INK4a, and the pro-apoptotic gene BIM. EBNA3C also interacts with the cellular protein IRF4, which promotes plasma cell differentiation and is an essential survival factor for activated B-cell lymphomas. The main goal of my research project is to determine if EBNA3A and EBNA3C are essential for tumorigenesis in the cord blood humanized mouse model viruses constructed by the Johanssen laboratory.