Warner Greene, MD, PhD

Laboratory of Molecular Immunology

Director, Gladstone Institute of Virology and Immunology
Nick and Sue Hellmann Endowed Professor of Translational Medicine
Professor, Departments of Medicine, Microbiology and Immunology
1650 Owens Street, Box 1230
San Francisco, CA 94158

(415) 734-4805 tel
Email

Lab website

Executive Assistant: Robin Givens
(415) 734-4805 tel

Description of Research

My laboratory focuses on the pathogenic interplay of the HIV-1 and HTLV-I human retroviruses with cells of the immune system and the diseases that may result, AIDS and the Adult T-cell Leukemia (ATL). Our current studies are exploring: 1) the molecular basis for action of the HIV Vif gene product and its interplay with APOBEC3G, a potent anti-retroviral cellular factor; 2) how HIV latency is maintained and new approaches to purging the virus from latent reservoirs; and 3) the biology of HIV in dendritic cells to better understand the molecular underpinnings of HIV transmission. 

A second part of the laboratory is studying the NF-kappaB/Rel family of transcription factors, which serve as "master regulators" of the immune and inflammatory responses. These investigations focus on the regulation of cytoplasmic and nuclear forms of NF-kappaB in normal cells as well as the participation of NF-kappaB/Rel in the evolution of HIV and HTLV-I induced disease and the function of NF-kappaB/Rel proteins in learning and memory.

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. We routinely use transgenesis and gene disruption technologies to elucidate 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 Genomics, Flow Cytometry, Microscopy, Histology, Transgenesis and Gene Disruption.

Some questions addressed in ongoing studies:
1. How does Vif overcome the potent innate antiviral activity of APOBEC3G?
2. How is APOBEC3G naturally regulated within cells?
3. How does HIV infect dendritic cells and how does "trans" infection of CD4 T cells occur?
4. How is HIV latency maintained and what approaches could be used to purge the virus from the latent reservoir?
5. How does HTLV-I Tax induce T-cell transformation and is its sustained expression required for the maintenance of the transformed state?
6. How does HIV cross the mucosal surface of the female genital tract and do different HIV clades display different efficiencies in this process?
7. Do HIV virions fuse with higher efficiency to specific subsets of human CD4 T cells and dendritic cells?
8. What are the various mechanisms responsible for intracellular regulation of the eukaryotic NF-kappaB transcription factor?
9.How do NF-kappaB/Rel proteins shape learning and memory?
10. What is the potential protective role of APOBEC3G in inhibiting the action of retroelements or “jumping genes” within the genome of human stem cells?

Cavrois M, Neidleman J, Kreisberg JF, Greene WC. In vitro derived dendritic cells trans-infect CD4 T cells primarily with surface-bound HIV-1 virions. PLoS Path. 3:e4, 2007.

Soros VB, Yonemoto W, Greene WC. Newly synthesized APOBEC3G is incorporated into HIV virions, inhibited by HIV RNA, and subsequently activated by RNase H. PLoS Path. 3:e15, 2007.

Stopak KS , Chiu Y-L, Kropp J, Grant RM, Greene WC. Distinct patterns of cytokine regulation of APOBEC3G expression and activity in primary lymphocytes, macrophages, and dendritic cells. J. Biol. Chem. 282:3589–3546, 2007.

Chiu YL, Witkowska HE, Hall SC, Santiago M, Soros VB, Esnault C, Heidmann T, Greene WC. High-molecular-mass APOBEC3G complexes restrict Alu retrotransposition. Proc. Natl. Acad. Sci. USA. 103:15588–15593, 2006.

O’Mahony A, Raber J, Foehr E, Montano M, Han V, Lu S, Kwon H, LeFevour A, Chakraborty-Sett S, Greene WC. NF- kB/Rel regulates inhibitory and excitatory neuronal function and synaptic plasticity. Mol. Cell Biol. 26:7283–7298, 2006.

Williams SA, Chen L-f, Kwon H, Ruiz-Jarabo CM, Verdin E, Greene WC. NF- kB p50 promotes HIV latency through HDAC recruitment and repression of transcriptional initiation. EMBO J. 25:139–149, 2006.

Chiu Y-L, Soros VB, Kreisberg JF, Stopak K, Yonemoto W, Greene WC. Cellular APOBEC3G restricts HIV-1 infection in resting CD4+ T cells. Nature 435:108–114, 2005.

Greene WC. The brightening future of HIV therapeutics. Nat. Immunol. 5:867–871, 2004.

Stopak K, de Noronha C, Yonemoto W, Greene WC. HIV-1 Vif blocks the antiviral activity of APOBEC3G by impairing both its translation and intracellular stability. Mol. Cell.12:591–601, 2003.

Chen L-f, Mu Y, Greene WC. Acetylation of RelA at discrete sites regulates distinct nuclear functions of NF-kB. EMBO J. 21:6539–6548, 2002.

Greene WC, Peterlin BM. Charting HIV's remarkable voyage through the cell: Basic science as a passport to future therapy. Nat. Med. 8:673–680, 2002.

Chen L-f, Fischle W, Verdin E, Greene WC. Duration of nuclear NF-kB action regulated by reversible acetylation. Science 293:1653–1657, 2001.

de Noronha C, Sherman MP, Lin HW, Cavrois M, Moir RD, Goldman RD, Greene WC. Dynamic disruptions in nuclear envelope architecture and integrity induced by HIV-1 Vpr. Science 294:1105–1108, 2001.

Geleziunas R, Xu W, Takeda K, Ichijo H, Greene WC. HIV-1 Nef inhibits ASK1-dependent death signalling providing a potential mechanism for protecting the infected host cell. Nature 410:834–838, 2001.