Washington University in St. Louis (WU)
Dr Ratner’s basic research is involved in a molecular dissection of virus-cell interactions. We focus on two retroviurses: Human T-Cell Leukemia Virus Type 1 (HTLV-1) which causes a specific form of lymphoma, and Human Immunodeficiency Viruses (HIV) Types 1 and 2. Our studies of HTLV-1 are concerned with analysis of the mechanisms of leukemogenesis through studies of: transforming determinants in an infectious immortalizing HTLV-1 proviral clone; transgenic models utilizing the HTLV-1 trans-activator protein, which results in a lymphoproliferative malignancy; and identification and characterization of the receptor for the virus. Our studies of HIV-1 focus on two distinct questions: 1) How does viral protein X (Vpx) enhance virus replication in quiescent cells? 2) How does the viral envelope interact with the receptor (CD4) and coreceptor (CXCR4 or CCR5) to allow virus entry? For these studies, we utilize infectious molecular clones of HIV-1 and HIV-2, cell culture and animal studies, small molecule and siRNA inhibitors, as well as viral and cellular cofactor mutants. Information from these studies has been applied to developing novel therapeutic approaches for HTLV-1 and HIV-1 infections. Dr Ratner’s clinical research is focused on human retrovirus-associated cancers. He has participated and/or led clinical trials HIV-associated lymphomas, anal carcinomas, and Kaposi’s sarcoma. He has also led multicenter trials of HTLV-1 associated leukemia/lymphoma.