My laboratory is involved in a molecular dissection of virus-cell interactions. We focus on two retroviruses: 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; translational and clinical studies of adult T cell leukemia in humans; and identification and characterization of the receptor for the virus.
Our studies of HIV-1 focus on two distinct questions: How do Gag proteins assemble to form a virus particle? These studies examine specific interactions between Gag proteins and the plasma membrane. In addition, we are examining the role of regulatory proteins that enhance virus assembly (Vpu) or are incorporated into the virus particle and enhance nuclear import of viral DNA (Vpx). What viral and cellular determinants regulate entry? For this project, we have mapped specific domains within envelope and co-receptor proteins that are critical for regulation of cell tropism.
Information from these studies has been applied to developing novel therapeutic approaches for HIV-1 infection.
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Localization of Vpx mutants by GFP fusion HeLa cell transfections visualized by fluorescent microscopy. Arrows point to cytoplasmic inclusion bodies.
From: Mahnke LA, Belshan M, Ratner L
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| 1973 | BA/MA (Chemistry), Harvard University, Cambridge, MA |
| 1979 | MD/PhD (Molecular Biochemistry and Biophysics), Yale University, New Haven, CT |
| 1979-1982 | Intern and Resident in Internal Medicine, Washington University, Barnes Hospital, St. Louis, MO |
| 1982-1983 | Medical Staff Fellow, Pediatric and Medical Oncology Branches, National Cancer Institute, National Institutes of Health, Bethesda, MD |
| 1983-1985 | Research Staff Fellow (Laboratory of Drs Flossie Wong-Staal and Robert Gallo), National Cancer Institute, National Institutes of Health, Bethesda, MD |
| 1985-1990 | Assistant Professor of Medicine, Washington University, St. Louis, MO |
| 1986-1990 | Assistant Professor of Molecular Microbiology, Washington University, St. Louis, MO |
| 1990-1993 | Associate Professor of Medicine and Molecular Microbiology, Washington University, St. Louis, MO |
| 1993-present | Professor of Medicine and Molecular Microbiology, Washington University, St. Louis, MO |
| 1995-present | Professor of Pathology, Washington University, St. Louis, MO |
| 2003-present | Director of Molecular Oncology |
| 1989-1992 | Washington University Medical School Communicable Disease Council |
| 1989-1992 | Washington University AIDS Committee |
| 1991-1996 | Washington University Biosafety Committee |
| 1992-1993 | Washington University Animal Biosafety Committee |
| 1993-1998 | Steering Committee for Molecular Genetics Graduate Program |
| 2002-present | Director, Cancer Biology Educational Program |
| 2002-present | Director, Oncology Fellowship Protocol Committee |
| 2005-present | Siteman Cancer Center Scientific Leadership Committee |
| 2007-present | Washington University School of Medicine Admissions Committee |
| 1987-1990 | Chairman, AIDS Clinical Trials Group Basic Research Committee |
| 1990-1995 | Member, AIDS Clinical Trials Group Core Oncology Committee |
| 1987-1995 | Scientific Advisory Board, American Foundation for AIDS Research |
| 1988-1989 | Protocol Chairman, AIDS ITP Study, ACTG 087 |
| 1991-1996 | AIDS Related Research Virology Study Section ARRC, DRG, NIH 1991-1996, Member 1994-1996, Chairman |
| 1995-1996 | Macrophage Culture SWAT Team, AIDS Clinical Trials Group |
| 2000-2003 | Co-Chair and Chair, Laboratory Working Group, AIDS Malignancy Consortium |
| 2005-present | European Union Virus-Associated Malignancies Grant Reviews |
| 2007-present | Veterans Administration Merit Grant Reviews in Infectious Diseases |
| 1987-1992 | AIDS Targeted Information Newsletter |
| 1987-present | AIDS Research & Human Retroviruses |
| 1988-present | Journal of the Acquired Immune Deficiency Syndrome |
| 1989-present | Virology |
| 1993-present | AIDS |
| 1995-present | Journal of Virology |
| 1983 | American Federation for Clinical Research |
| 1983 | American Society for Microbiology |
| 1983 | American Association for the Advancement of Sciences |
| 1986 | American Association of Cancer Reseerach |
| 1987 | American Society of Hematology |
| 1987 | American Society of Clinical Oncology |
| 1988 | International AIDS Society |
| 1990 | American Society for Clinical Investigation |
| 1990 | American Society for Virology |
| 1992 | International Society for Antiviral Research |
| 1993 | International Society for Human Retrovirology |
| 1995 | American College of Physicians, Fellow |
| 1997 | Association of American Physicians |
| 1997 | American Foundation for AIDS Research, Scientific Advisory Board |
| 1982 | Internal Medicine |
| 1985 | Medical Oncology |
| 1985 | American Federation for Clinical Research Trainee Award |
| 1985 | Coleman/Fannie Mae Candies Foundation Fellowship Award |
| 1985 | John A & George L Hartford Foundation Fellowship Award |
| 1986 | American Society of Clinical Oncology Young Investigator Award |
| 1990 | American Cancer Society Faculty Research Award |
| 2001 | Lifetime Achievement Award for Studies of Human T Cell Leukemia Viruses, International Conference on Human Retrovirology, Dublin |