Warner C. Greene, M.D. Ph.D. Director and Senior Investigator Nick and Sue Hellmann Distinguished Professor of Translational Medicine Gladstone Institute of Virology and Immunology Professor of Medicine, Microbiology and Immunology University of California, San Francisco Email: wgreene@gladstone.ucsf.edu Telephone: 415-734-4805 Fax: 415-355-0153
Areas of Investigation My laboratory focuses on the pathogenic interplay of the HIV-1 and HTLV-I human retroviruses with immune cells. Infection of human hosts with these retroviruses produces contrasting diseases within the CD4 subset of T lymphocytes, specifically the Acquired Immune Deficiency Syndrome (AIDS) with HIV-1 and the Adult T-cell Leukemia (ATL) with HTLV-1. Their studies explore the molecular biology of the HIV Vif, Nef and Vpr gene products as well as the transforming properties of HTLV-I Tax. More recently, we have begun to study HIV and HTLV-1 Env-mediated fusion and the mechanisms underlying transmission of HIV across the female genital mucosa.
We continue to also pursue our longstanding interest in the biology of the NF-kB/Rel family of transcription factors, which serve as "master regulators" of the immune and inflammatory responses. These studies currently focus on the role of these transcription factors as major antagonists of HIV latency.
Significance My laboratory seeks to understand the molecular basis for HIV and HTLV-I retroviral pathogenesis. Through the insights gained from these studies, we hope to contribute to the development of new therapeutic approaches for these fatal retrovirus-induced diseases. Similarly, our studies of NF-kB are not only aimed at unraveling how this powerful transcription factor is regulated, but also at developing new strategies for intervening in unwanted inflammatory and immune reactions mediated by NF-kB.
Approaches
Due to the broad scope of experimental questions, we employ a wide range of molecular, biochemical, cell biological and immunological techniques to study HIV and HTLV-I pathogenesis. Individuals completing training in the laboratory routinely acquire expertise in all of these areas. Increasingly, we are utilizing transgenesis and gene disruption approaches to study the function of specific genes in vivo. Our studies often take advantage of the outstanding core services offered at the Gladstone Institutes including cores in Virology, Immunology, Genomics, Flow Cytometry, Microscopy, Histology, Transgenesis and Gene Disruption.
Contributions
A list of scientific advances made by members of the laboratory and the relevant citations for this work is presented in the "Past Contributions" section of this home page.
Some questions addressed in ongoing studies
How does Vif overcome the potent innate antiviral activity of APOBEC3G?
How does HIV Nef accelerate viral pathogenesis?
How does HIV Vpr induce G2 cell cycle arrest and does such derangement of the cell cycle occur in HIV infected patients?
What are the signals that promote nuclear import of the HIV preintegration complex?
How does HTLV-I Tax induce T cell transformation and is its sustained expression required for the maintenance of the transformed state?
How does HIV cross the mucosal surface of the female genital tract and do different HIV clades display different efficiencies in this process?
Do HIV virions fuse with higher efficiency to specific subsets of human CD4 T cells and dendritic cells?
What are the various cellular mechanisms and post-translational modifications responsible for regulating the expression and action of the eukaryotic NF-kB/Rel family of transcription factors?
What cellular signaling process contributes to the role that NF-kB/Rel transcription factors play in HIV latency?
What role do the various NF-kB/Rel transcriptional regulators play in regulating human embryonic stem cell (hESC) pluripotency versus differentiation?
What are the events that regulate the actvation of NF-kB/Rel in the brain and how does the action of this factor impact on normal versus disease-related neuronal function?
Warner C. Greene, M.D. Ph.D.