Dr. Edward Browne, associate professor of medicine leading the Browne Lab within the HIV CURE Center, focuses on developing methods for studying and eliminating the latent HIV reservoir from infected patients. Latently infected cells are resistant to current HIV therapies and can persist in infected patients for decades. He recently received two NIH awards.
Transcriptional inactivation of the CNS HIV reservoir with Tat-targeting lipid nanoparticles
New cure approaches are needed that promote permanent silencing or inactivation of viral gene expression. In particular, the viral protein Tat plays a central role in driving viral gene expression, and secretion of Tat from infected microglia likely contributes to CNS toxicity and HIV-associated neurocognitive disorder (HAND). Thus, irreversibly inhibiting or inactivating Tat in brain resident microglia could represent an effective way to block viral reactivation and to limit virus-induced HAND. However, no antiviral drugs that target Tat or viral transcription are currently available for clinical use. This new R01 will target the HIV reservoir in the brain with CRISPR-delivering nanoparticles. This project will develop a lipid nanoparticle tool to inactivate the HIV Tat gene in vivo using CRISPR. Funded by the NIH–National Institute on Drug Abuse. Read more.
Defining the impact of cannabinoids on the HIV reservoir in humanized mice
Cannabis (CB) use is prevalent amongst people with HIV (PWH), but its impact on HIV infection, immunity and the latent viral reservoir is unknown. In this proposal, the team will develop a humanized mouse model of HIV infection and CB use (R61) and detail the impact of CB exposure on HIV reservoir size, latency reversal, and molecular phenotype of infected cells in within the CNS (brain) and periphery (spleen) of ART suppressed humanized mice (R33). Funded by the NIH–National Institute of Allergy and Infectious Diseases. Read more.