Richard F. Ambinder, M.D., Ph.D.
Primary Appointment in Oncology; Secondary Appointments in Pathology, Pharmacology and Molecular Sciences
Member, Graduate Program in Biochemistry, Cellular and Molecular Biology; Member, Graduate Program in Pharmacology and Molecular Sciences
Epstein-Barr virus is consistently found in association with a variety of tumors including African Burkitt's lymphoma, nasopharyngeal carcinoma, mixed cellularity Hodgkin's disease, post-transplant lymphoma, and AIDS central nervous system lymphoma. Our laboratory studies are aimed at better defining the role(s) of the virus in the pathogenesis of these diseases and the development of strategies to diagnose and treat those malignancies. For example, is there a way to utilize the presence of the virus to specifically target therapy? In patients with EBV-associated Hodgkin's disease, every tumor cell (identified morphologically or by double labeling with CD30) carries the viral genome and expresses the latency membrane protein-1(LMP-1). In non-malignant tissues (including lymph nodes and spleen), there are very few EBV-infected cells and none express LMP-1. In approximately 1/3 of normal volunteers, cytotoxic T cell activity directed against LMP-1 can be detected. Cytotoxic T cells against other EBV antigens are much more common. Cytotoxic T cells directed against EB nuclear antigens (EBNA's)-3A, -3B and -3C can be detected in virtually all normal volunteers. However, these antigens are not expressed in EBV-associated Hodgkin's disease. Can cytotoxic T cells which specifically recognize viral antigens expressed in tumor cells be induced with a therapeutic vaccine, or expanded in vitro from an HLA-matched allogeneic donor and infused in the setting of bone marrow transplantation? Can highly immunogenic viral genes that are not expressed in tumors be induced pharmacologically so as to lead to expression and consequent immune destruction of tumorous cells? Can immuno-suppressive viral gene products such as viral IL-10 be turned off with inhibitors of viral late gene expression and thus render patients more immune competent?
Moore SM, Cannon JS, Tanhehco YC, Hamzeh FM, Ambinder RF. Induction of Epstein-Barr Virus Kinases to Sensitize Tumor Cells to Nucleoside Analogues. Antimicrob Agents Chemother. 45:2082-2091, 2001.
Murray PG, Swinnen LJ, Flavell JR, Ragni MV, Baumforth KRN, Toomey SM, Filipovich AH, Lowe D, Schnell CS, Young LS, Ambinder RF. Frequent Expression of the Tumor Necrosis Factor Receptor-Associated Factor 1 in Latent Membrane Protein 1-Positive Posttransplant Lymphoproliferative Diseaseand HIV-Associated Lymphomas. Hum Path, 32:963-969, 2001.
Gulley ML, Glaser SL, Craig FE, Borowitz M, Mann RB, Shema SJ, AmbinderRF. Guidelines for interpreting EBER in situ hybridization and LMP1 immunohistochemical tests for detecting Epstein-Barr virus in Hodgkin Lymphoma. Am J Clin Path, 117:259-267, 2002.
Tao Q, Yang J, Swinnen LJ, Ambinder RF. Conservation of Epstein-Barr VirusCytotoxic T Cell Epitopes in Post transplant Lymphomas: Implications for Immune Therapy. Am J Pathol 160:1839-45, 2002.