Current antiretroviral therapy (ART) is effective in the suppression of HIV replication but failed to eliminate latent HIV reservoirs. Our lab aims to discover the molecular mechanisms how HIV transcription machinery is regulated during active HIV transcription and during the establishment of latency. The ultimate goal is to translate our understanding of transcription and latency of HIV into therapeutic interventions.
Epigenetic Regulation of HIV Transcription and Latency
We recently discovered that a previously unrecognized epigenetic modification called histone crotonylation is involved in an efficient transcription of HIV. The induction of crotonylation disrupted HIV latency. In combination with other latency reversal agents (LRAs), the disruption of HIV latency is highly achieved compared with a single LRA. We are particularly interested whether and how crotonylation of histone and non-histone proteins regulates other signaling pathways to directly modulate HIV transcription or latency.
Deep Silencing for a Functional Cure of HIV
We recently established a novel HIV deep latency model in which not only a deep latency of HIV can be induced but also sustained. We are actively investigating the molecular mechanisms underlying the induction and maintenance of deep latency and extending it to patient models to deeply silence HIV proviruses and prevent viral rebound.
HIV Tissue Reservoirs
We are interested in how cells in tissues are infected by HIV, such as CNS, placenta, kidney, GALT and skin. For example, how the unique interaction among HIV, immune cells, vascular cells, and neuronal cells contributes to the initial seeding of HIV reservoirs in the CNS, and whether we can target the unique viral infection and latency signaling pathways to attack HIV reservoirs in the CNS, thereby controlling HIV infection and HIV-associated neurocognitive disorders (HAND). We will examine it in HIV-infected rhesus macaques, transgenic HAND mouse model and brain tissues from PLWH.
Our lab is actively supported by Qura Therapeutics, UNC Center for AIDS Research, NIMH and CARE Program.