The research focus of my laboratory is understanding the biology of HIV-1 virus-host interplays that enable establishment of viral latency and persistence during anti-retroviral therapy. Currently, I have two major research projects in the lab.

1. HIV-1 reservoirs: virologic and immunologic implications.

A major challenge in HIV-1 research is the inability to eliminate tissue-resident reservoir cells that continue to harbor the virus during treatment. My research focuses on characterization of one such HIV-1 reservoir, lung alveolar macrophages (AMs). For this study, AMs from patients living with HIV-1 are obtained through an international collaboration with scientists at the Malawi-Liverpool-Wellcome Clinical Research Program at Blantyre, Malawi. Our research has revealed that HIV-1 remains transcriptionally active in AMs even after long-term therapy. This finding has challenged the traditional perception of viral latency as a transcriptionally-silent state. We are further investigating the molecular mechanisms of this "active" viral persistence in HIV-1 infected lung AMs by in-depth analysis of the viral genomic and transcriptomic landscapes in untreated and anti-retroviral treated individuals as well as their functional impacts on lung immunity. Our research aims to provide fundamental scientific knowledge about this new layer of complexity in HIV-1 persistence and devise tailored strategies to eliminate these myeloid reservoir cells.

2. Long non-coding RNAs in HIV-1 infection: discovery, functional characterization and clinical relevance.

Advances in next-generation sequencing techniques have unveiled long non-coding RNAs (lncRNAs) as the largest class of RNAs that are transcribed from the human genome. Although lncRNAs do not code for proteins; they have shown remarkable versatility in their functions with roles in almost every aspect of the biological processes. A second area of my research is focused on elucidating the roles of lncRNAs as novel host-dependency factors in HIV-1 replication and/or latency. The newly identified lncRNAs are further interrogated for their molecular mechanisms of function as well as their relevance as potential targets of host-directed therapy against HIV-1.

We employ cutting-edge molecular virology, immunology and genomics techniques in both ex vivo clinical samples and in vitro systems of HIV-1 infection for our studies. Our scientific motivation and long-term goals are to identify the cellular and viral vulnerabilities in latent or persistently infected cells that can be exploited for the development of new therapeutic interventions towards a cure for HIV-1.