I joined Washington University in July of 1985. I graduated from Yale University in 1979 and trained in Internal Medicine at Barnes Hospital. After completing Medical Oncology training at the National Cancer Institute, I worked as a research associate with Drs. Flossie Wong-Staal and Robert Gallo. My laboratory is studying human retrovirus infections.
My basic research is focused on the genetic basis of HTLV-1 lymphomagenic activity. This includes basic molecular biology studies, animal models, and multicenter clinical trials. My interests in HTLV-1 began during postdoctoral studies in 1983, and my independent laboratory has been critical in establishing a strong molecular understanding of the pathogenic effects of this virus over the last 29 yrs. 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. We established the first infectious molecular clone of HTLV-1 and the first animal model of HTLV-1-associated leukemia-lymphoma. These tools have been provided to almost every group in the field throughout the world since their discovery, and a number of current innovative variations of these reagents include studies of the pathogenesis of the infectious molecular clone in humanized mice and an inducible transgenic mouse model of HTLV-1 Tax induced lymphoma. The major focus over the last 10 yrs has been deciphering the role of Tax activation of NFκB in lymphoma.
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. Information from these studies has been applied to developing novel therapeutic approaches for HTLV-1 and HIV-1 infections.
My clinical research is focused on human virus-associated cancers. I participated and/or led clinical trials HIV-associated lymphomas, anal carcinomas, and Kaposi’s sarcoma. I have also led multicenter trials of HTLV-1 associated leukemia/lymphoma.
I am Co-Director of Molecular and Medical Oncology with combined faculty of 34 individuals. I am PI of the NCI T32 funded Molecular Oncology Training Program, and Co-Leader of the Solid Tumor Therapeutics Research Program of the Siteman Cancer Center. I am a former American Cancer Society Research Professor. I mentored 16 graduate students (4 were MD PhD students) who completed their thesis and 41 postdoctoral researchers have trained in my laboratory (of whom 5 had both MD PhD, 6 had MD, and 1 had DVM and PhD degrees). I sponsored postdoctoral trainees who successfully competed for F32 National Research and K08 Clinical Investigator Awards, and fellowship/scholar grants from the Leukemia Society, Keck Foundation, Lymphoma Research Foundation, and American Foundation for AIDS Research.