Warner C. Greene, MD, PhD

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

President, Accordia Global Health Foundation

Executive and Administrative Assistants

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

Sue Cammack, 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 the pathogenic effects of HIV infection, with special emphasis on the function of the HIV nef, vif, and vpr gene products. He is the author of more than 350 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.

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

President, Accordia Global Health Foundation

Executive and Administrative Assistants

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

Sue Cammack, 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 therapy. Currently, we are exploring 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 are focusing 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 various host proteins like 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. Other studies are examining how two different amyloid fibrils found in human semen propel HIV infection by promoting virion attachment to target cells. 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 attempting to identify viral determinants that are associated with heightened transmission at mucosal surfaces. Finally, we are examining the role of the APOBEC3 family of cytidine deaminases in both the restriction of exogenous retroviruses like HIV and the inhibition of endogenous retroelements like LINE1 in human embryonic stem cells and induced pluripotent stem cells (iPSCs) where LINE-1 expression is greatly increased. 

Current Lab Focus

• How does abortive HIV infection of bystander CD4 T lymphocytes promote their death?

• What are the DNA sensor(s) involved in this death pathway?

• What is the precise mechanism of cell death?

• Is this abortive infection-cell death pathway not operating in non-pathogenic lentiviral infections involving natural hosts?

• Why are circulating peripheral blood CD4 T cells resistant to this form of HIV-induced cell death?

• Does the inflammation associated with CD4 T cell death contribute to the accelerated appearance of aging diseases in HIV-infected subjects?

• Do the SEVI and semenogelin-derived amyloid fibrils enhance HIV transmission in vivo?

• Do these two amyloid fibrils normally enhance fertilization?

• Does the reprogramming of skin cells into iPS cells lead to genomic injury as a result of heightened retrotransposition of endogenous mobile genetic elements?

• What cellular defenses are in action of stem cells to curtail the threat of these mobile genetic elements?

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 death, for these non-permissive cells.

• Showed that semen contains at least two distinct amyloid fibrils that greatly increase HIV infection in vitro.

• 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

• Washington University in St. Louis Alumni Achievement Award (2012)
• President-Elect, American Association of 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)