Lucio Gama, PhD
Director for Scientific Collaborations at the Vaccine Research Center, National Institutes of Health
Miller Research Building, room 809
University of São Paulo, Brazil
University of São Paulo, Brazil
Dr. Lucio Gama is an Assistant Professor in the Department of Molecular and Comparative Pathobiology at The Johns Hopkins School of Medicine with expertise in virology, molecular biology, and immunology – more specifically in HIV/SIV and myeloid cells. He have worked in the Retrovirus Laboratory for 14 years investigating innate immune responses during SIV infection, coordinating several research projects, and co-mentoring undergraduate and graduate students. In 2009, while studying phenotypic variations in myeloid cells during HIV and SIV infection, he identified a novel monocyte subpopulation that suppresses CD8+ T cell proliferation during SIV and HIV acute infection. Following these findings, Dr. Gama started collaborating with other research groups at Johns Hopkins and abroad, studying changes in monocyte phenotypes in the context of HIV, dengue, HTLV-1 infection, and atherosclerosis. In addition, Dr. Gama has been developing in vitro models for the study of HIV and SIV latency/reactivation in monocytes and tissue macrophages. Most recently he demonstrated for the first time that brain macrophages in SIV-infected ART-treated macaques harbor silent viral genomes that can be reactivated by latency reversing agents.
Characterization of myeloid cell subsets in SIV and HIV infection:
As Dr. Gama started analyzing blood leukocytes in the macaque model, he identified and characterized the expansion of a novel immunosuppressive subset of phenotypically distinct monocytes (CD14high CD16neg CCR2low/neg) during acute SIV infection. In collaboration with Dr. Esper Kallás (University of São Paulo, Brazil), he identified similar subset in samples isolated from HIV-infected cART-naïve patients. This discovery was not only important for the evaluation of immunosuppressive mechanisms in HIV infection, but also added to recent findings in monocyte differentiation. Also, in collaboration with Dr. Janice Clements, he developed new tools for the characterization and quantitation of residents SIV+ macrophages in our SIV macaque model. These innovative tools helped substantiate the hypothesis that macrophages can serve as latent SIV reservoirs and therefore should be thoroughly considered during AIDS cure strategies.
Characterization of agents to reverse HIV and SIV latency during “shock and kill” strategies:
Current combination antiretroviral therapies for HIV-infected patients can reduce plasma viral load to undetectable levels but do not eliminate virus reservoirs. New strategies for viral eradication have been investigated, including the administration of compounds to reactivate latent viral genomes in infected cells, which then could be eliminated by the immune system (“Kick and Kill”). In 2012, Dr. Gama started collaboration with scientists in Brazil who were developing semisynthetic drugs for the activation of latent reservoirs. One of these compounds, a diterpene named ingenol-3-hexanoate (Ing-B), was tested in the Retrovirus laboratory and now it’s been used as a proof of concept to demonstrate the efficacy and safety of PKC activators during kick and kill. He has now developed tools to evaluate the efficacy of such agents in macrophages latently infected with SIV and HIV.
- Avalos CR, Abreu CM, Queen SE, Li M, Price S, Shirk EN, Engle EL, Forsyth E, Bullock BT, Mac Gabhann F, Wietgrefe SW, Haase AT, Zink MC, Mankowski JL, Clements JE, Gama L. Brain Macrophages in Simian Immunodeficiency Virus-Infected, Antiretroviral-Suppressed Macaques: a Functional Latent Reservoir. MBio. 2017 Aug 15;8(4).
- Shirk EN, Kral BG, Gama L. Toll-like receptor 2bright cells identify circulating monocytes in human and non-human primates. Cytometry A. 2017 Apr;91(4):364-371.
- Gama L, Abreu CM, Shirk EN, Price SL, Li M, Laird GM, Pate KA, Wietgrefe SW, O'Connor SL, Pianowski L, Haase AT, Van Lint C, Siliciano RF, Clements JE. Reactivation of simian immunodeficiency virus reservoirs in the brain of virally suppressed macaques. AIDS. 2017 Jan 2;31(1):5-14.
- Russell JN, Clements JE, Gama L. Quantitation of gene expression in formaldehyde-fixed and fluorescence-activated sorted cells.. PLoS One. 2013 Sep 2;8(9):e73849.
- Gama L, Shirk EN, Russell JN, Carvalho KI, Li M, Queen SE, Kalil J, Zink MC, Clements JE, Kallas EG. Expansion of a subset of CD14highCD16negCCR2low/neg monocytes functionally similar to myeloid-derived suppressor cells during SIV and HIV infection. J Leukoc Biol. 2012 May;91(5):803-16.