Warner C. Greene, MD, PhD

Director and Senior Investigator

Nick and Sue Hellmann Distinguished Professor of Translational Medicine

Phone: (415) 734-4805
Fax: (415) 355-0153
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Other Professional Titles

Investigator, Roddenberry Stem Cell Center for Biology and Medicine at Gladstone

Professor, Medicine, Microbiology and Immunology, University of California, San Francisco

Co-Director, UCSF-GIVI Center for AIDS Research

Executive Chairman, Accordia Global Health Foundation

Executive and Administrative Assistants

Robin Givens, Senior Executive Assistant
(415) 734-4805
rgivens@gladstone.ucsf.edu

Sue Cammack, Senior Administrative Assistant
(415) 734-4806
scammack@gladstone.ucsf.edu

More about Dr. Greene

The ongoing research in Dr. Greene’s laboratory focuses on the molecular mechanisms underlying HIV pathogenesis, latency, and transmission. He is the author of more than 366 scientific papers and has been recognized as one of the 100 Most Cited Scientists in the world.

After serving as a Senior Investigator at the National Cancer Institute and a Professor of Medicine and Howard Hughes Investigator at Duke University Medical Center, Dr. Greene accepted his current position as the Founding Director of the Gladstone Institute of Virology and Immunology in 1991.

Dr. Greene is a member of the Institute of Medicine of the National Academies and a fellow of the American Academy for the Advancement of Science. He also serves as Co-Director of the UCSF-GIVI Center for AIDS Research, and has served as a councilor and president of the Association of American Physicians.

In 2013, Dr. Greene became the executive chairman of the Accordia Global Health Foundation, whose mission is to overcome the burden of infectious diseases by building healthcare capacity and strengthening academic medical institutions in Africa.

Dr. Greene earned a bachelor’s degree at Stanford University and an MD/PhD at Washington University School of Medicine. He took his internship and residency training in Medicine at the Massachusetts General Hospital at Harvard.

More scientific details, please

Other Professional Titles

Investigator, Roddenberry Stem Cell Center for Biology and Medicine at Gladstone

Professor, Medicine, Microbiology and Immunology, University of California, San Francisco

Co-Director, UCSF-GIVI Center for AIDS Research

Executive Chairman, Accordia Global Health Foundation

Executive and Administrative Assistants

Robin Givens, Senior Executive Assistant
(415) 734-4805
rgivens@gladstone.ucsf.edu

Sue Cammack, Senior Administrative Assistant
(415) 734-4806
scammack@gladstone.ucsf.edu

Areas of Investigation

My laboratory seeks to better understand the pathological interplay of human retroviruses like HIV and HTLV with their cellular hosts with the goal of providing new approaches for prophylaxis and therapy. A major focus of the lab is understanding how HIV promotes CD4 T-cell death. We have shown that most CD4 T cells die as a result of an innate immune response launched against cytoplasmic viral DNA accumulating as a result of abortive infection in these “bystander” CD4 T cells. Other studies in the laboratory focus on the molecular mechanisms underlying HIV latency including a role for host proteins and miRNAs that reinforce the latent state as well as the action of host proteins such as NF-kB that antagonize latency. Ultimately, we hope to contribute to efforts to develop a combination of inducing agents that can effectively purge virus from the latent reservoir. A third area of investigation examines how factors in human semen, in particular HIV-binding amyloid fibrils, propel HIV infection. We seek to better understand the role of these factors in HIV transmission and to design novel inhibitors against these fibrils that could be coupled with antiviral drugs to create a new class of more effective combination microbicides. In a related area of investigation, we are identifying viral determinants that are associated with heightened transmission at mucosal surfaces. Finally, we are delineating the innate immune signaling pathways governing the antiviral restriction activities of SAMHD1. 

Current Lab Focus

  • What are the mechanisms occurring during cell-to-cell transmission of HIV that are required to elicit CD4 T-cell death?
  • How does abortive HIV infection of bystander CD4 T lymphocytes promote their death?
  • Is this abortive infection and pyroptotic cell death not operating in non-pathogenic lentiviral infections of natural hosts?
  • Why are circulating peripheral blood CD4 T cells resistant to this form of HIV-induced cell death?
  • What is the effect of the HIV-2 accessory protein Vpx on HIV infectivity and the cell death pathway in lymphoid CD4 T cells?
  • Does the inflammation associated with CD4 T-cell death contribute to the accelerated appearance of aging diseases in HIV-infected subjects?
  • Do the semen-derived amyloid fibrils enhance HIV transmission in vivo?
  • What viral and host factors affect HIV transmission in the genital mucosa?
  • How do long-range chromatin interactions affect the establishment and maintenance of HIV latency?
  • Which cellular microRNAs are involved in reinforcing HIV latency?
  • How is the antiviral activity of SAMHD1 regulated?
  • What are the mechanisms by which the host factor SAMHD1 restricts HIV reverse transcription?

 

Joined Gladstone

1991

Why Gladstone?

I was recruited as the founding director of the Gladstone Institute of Virology and Immunology. I set out to build a team that could attack the threat posed by the HIV/AIDS epidemic from many different angles. I believed that a multidisciplinary approach, firmly rooted in basic science, could make a important contribution in the battle against HIV/AIDS.

Key Achievements

  • Demonstrated that unsuccessful HIV infection of “bystander” CD4 T cells results in an accumulation of abortive HIV reverse transcripts that elicit innate antiviral and inflammatory responses and cell death in non-permissive cells.
  • Demonstrated that abortively infected cells activate caspase-1 to produce a fiery cell death known as pyroptosis, causing significant inflammation as they release their entire cytoplasmic contents, including inflammatory cytokines, into the extracellular space.
  • Identified interferon-gamma–inducible protein 16 (IFI16) as a host DNA sensor required for CD4 T-cell death due to abortive HIV infection.
  • Showed that semen contains at least two distinct amyloid fibrils that greatly increase HIV infection in vitro.
  • Established a Jurkat cell model of HIV latency (5A8 cells) that is inducible by T-cell receptor cross-linking and displays drug reactivation profiles resembling that from resting CD4 T cells from aviremic patients. These cells could be conveniently used for high-throughput screening for novel HIV anti-latency compounds.
  • Demonstrated that Vif subverts the antiviral activity of APOBEC3G by promoting its degradation in the 26S proteasome and by impairing its synthesis.
  • Demonstrated that ABOBEC3G, in conjunction with RNA granules, functions to regulate endogenous mobile genetic elements (e.g., Alu RNAs), whose mobility contributes to a variety of human diseases including cancers and leukemias.
  • Discovered that APOBEC3 encodes Rfv3, a gene influencing production of neutralizing antibody responses in retrovirus infection.
  • Discovered that HIV-1 virions transmitted in trans from dendritic cells to T cells principally involves virions located on the surface of DCs instead of internalized virions.
  • Demonstrated that laboratory-adapted CCR5-tropic 81A virions fuse rapidly and efficiently to immature MDDCs, whereas NL4-3, the isogenic CXCR4-tropic counterpart of 81A, fuse slowly and inefficiently to both immature and mature MDDCs.
  • Identified NF-κB as a modulator of inhibitory tone in the brain by regulating expression of GAD65 in inhibitory GABAergic interneurons.
  • Discovered NF-κB p50/HDAC1 as a transcriptionally repressive complex promoting HIV-1 latency.
  • Showed that Vpr can disrupt nuclear envelope architecture and integrity.
  • Cloned first cytokine receptor (alpha chain of IL-2 receptor).
  • Demonstrated that IκBα undergoes stimulus coupled degradation and that the activation of NF-κB in turn induces de novo IκBα synthesis.
  • Showed that acetylation/deacetylation of RelA subunit of NF-κB functions as an intranuclear switch controlling both the magnitude and duration of its transcriptional response.
  • Demonstrated that HIV Nef inhibits ASK-1 dependent death signaling providing a mechanism for protecting infected cells from premature death.
  • Described deregulated expression of IL-2 receptors on HTLV-I induced adult T cell leukemia lymphocytes.
  • Described how p50 subunit of NF-κB is generated by a cotranslational action of the proteasome.

Education

Stanford University (BA), Graduated with Great Distinction (1971)
Washington University School of Medicine (MD, PhD), Graduated with Honors (1977)

Affiliations

American Federation for Clinical Research
American Association of Immunologists
American Association of Physicians
American College of Physicians
American Rheumatism Association
American Society for Microbiology
American Society for Cell Biology
American Society for Clinical Investigation
Association of American Physicians
California Academy of Medicine
Mayor’s AIDS Scientific Advisory Council, San Francisco
Academic Alliance Foundation
AIDS Memorial Advisory Board
American Association for the Advancement of Science
Institute of Medicine of the National Academies
Global Virus Network
Center for AIDS Research, University of Alabama at Birmingham

Editorial Board, The New Biologist
Editorial Board, Cytokine
Editorial Board, AIDS Research and Human Retroviruses
Editorial Board, Molecular Biology of the Cell
Editorial Board, Academic Press “InScight” Internet News Service
Editorial Board, Journal of Acquired Immune Deficiency Syndrome
Editorial Board, Retrovirology
Editorial Board, Cell Host & Microbe

Awards

  • Member American Academy of Arts and Sciences (2014)
  • Tim Gill Distinguished Lecturer, University of Colorado Denver (2014)
  • Francis Gilman Blake Award, Association of American Physicians (2013)
  • Avant-Garde Award, National Institutes of Health (2013)
  • Washington University in St. Louis Alumni Achievement Award (2012)
  • President, Association of American Physicians (2012)
  • President-Elect, Association of American Physicians (2011)
  • Center Director, Global Virus Network (2011)
  • Invited Speaker, Washington University MSTP 40th Anniversary Symposium (2010)
  • Distinguished Leader in Medicine Lecture, Dalhousie University (2009)
  • Interview Panelist, NIH Director’s Pioneer Award (2009)
  • Lecturer, Royal Society, Cytidine Deaminases (2008)
  • Co-Chair, NIAID Summit on HIV Vaccine Research and Development, Bethesda, MD (2008)
  • Nick and Sue Hellmann Distinguished Professor of Translational Medicine (2006)
  • Review Committee, NIH Director’s Pioneer Award Program (2006)
  • Elected to the Institute of Medicine of the National Academies (2005)
  • Councilor, Association of American Physicians (2005)
  • Elected Fellow, American Association for the Advancement of Science (2004)
  • Honorary Co-Chair, AIDS Memorial Advisory Board (2003)
  • Board of Directors, Academic Alliance Foundation (2003)
  • Selected as Original Member, ISI Highly Cited Researchers (2001)
  • Executive Committee, Scientific Advisory Board of the Institute of Human Virology (1999)
  • Elected to California Academy of Medicine (1993)
  • Elected to Association of American Physicians (1990)
  • Recipient, Young Investigator Award of the American Rheumatism Association (1988)
  • Recipient, Outstanding Investigator Award from the American Federation for Clinical Research (1987)
  • Elected to American Society for Clinical Investigation (1985)
  • Washington Academy of Sciences Award in the Biological Sciences (1984)
  • St. Louis Internists Prize in Medicine (1977)
  • Sigma Xi Research Honorary (1976)
  • California Heart Association Research Fellowship Award (1970)
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Featured Publications

Warner C. Greene, MD, PhDRoan NR, Müller JA, Liu H, Chu S, Arnold F, Stürzel CM, Walther P, Dong M, Witkowska HE, Kirchhoff F, Münch J, Greene WC. Peptides Released by Physiological Cleavage of Semen Coagulum Proteins Form Amyloids that Enhance HIV Infection. Cell Host Microbe. 2011 Dec 15; 10(6):541-50. View in: PubMed
Warner C. Greene, MD, PhDRoan NR, Sowinski S, Münch J, Kirchhoff F, Greene WC. Aminoquinoline surfen inhibits the action of SEVI (semen-derived enhancer of viral infection). J Biol Chem. 2010 Jan 15; 285(3):1861-9. View in: PubMed