Recipient, Early Career Research Excellence Award - Basic Science (2019)
Andrea Gramatica is a scientist in Warner Greene’s laboratory at the Gladstone Institute of Virology and Immunology. His research focuses on finding new ways to reduce the size of the latent HIV-reservoir with a therapeutic approach called “shock and kill.” This method aims to utilize small-molecule compounds, named latency-reversing agents (LRAs), to induce reactivation of quiescent, non-replicating virus in CD4 T cells. Dr. Gramatica has identified a new class LRAs that efficiently reverse latency ex vivo in CD4 T cells isolated from HIV-positive individuals on suppressive antiretroviral treatment (ART). These LRAs are non-toxic, non- inflammatory and, remarkably, preserve cytotoxic effector functions of CD8 T and NK cells, thereby potentially allowing clearance of the viral reservoir in chronically infected patients.
Dr. Gramatica received his PhD in Cell Biology from the Humboldt University of Berlin (Germany), where he studied the interactions between the HIV-1 structural protein Gag and intracellular calcium-modulated pathways, and developed an innovative nanomedical system, based on immunoliposomes, for in vitro clearance of HIV-particles by macrophages.
Spotlight: 2019 CFAR Excellence Award Recipient — Basic Science
The existence of the HIV reservoir represents a major barrier to HIV cure: Latently infected CD4 T cells express little or no viral antigens and are therefore invisible to the immune system. Once “re-activated,” however, infected CD4 T cells can be targeted for elimination by neutralizing antibodies or by host CD8 T and NK cells. Although the LRAs studied so far in the field have been proven too toxic for in vivo applications (especially toward CD8 T and NK cells), Gramatica has identified a new class of LRAs that reverse latency ex vivo with no toxic effects. “Activation of the proviral promoter is tightly connected to cellular proliferation and metabolic activation of CD4 T cells,” he explains, “By hijacking the signaling cascades that regulate glycolysis, we can antagonize latency while inducing survival signals, thereby avoiding broad toxic effects.”
The reservoir is the target for a cure, and in his current work, in collaboration with Dr. Louis Picker’s lab at the Oregon Health & Science University, Andrea Gramatica is investigating whether one of the LRAs he has identified can antagonize latency in vivo in SIV-infected rhesus monkeys on suppressive ART.
Growing up in Milan, Italy, Andrea moved to Berlin in 2009 where he completed his Master’s degree in Industrial Biotechnology, followed by a PhD in Cell Biology at the department of Molecular Biophysics at Humboldt University of Berlin. Andrea moved to San Francisco in 2015. Since then, he has enjoyed exploring the natural wonders of Northern California and spending his free time watching and learning about film.