BIG PICTURE RESEARCH TOPICS
Our current projects are aimed at mechanistically understanding the early events in the lifecycle of the major human pathogens HIV-1 and HIV-2. We utilize molecular, cellular, biochemical, and evolutionary techniques to better understand these lentiviruses. We are interested in asking fundamental questions such as:
Our current projects are aimed at mechanistically understanding the early events in the lifecycle of the major human pathogens HIV-1 and HIV-2. We utilize molecular, cellular, biochemical, and evolutionary techniques to better understand these lentiviruses. We are interested in asking fundamental questions such as:
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There are currently two main tracks that we are working on in the lab:
Understand the role of the DNA damage response in the lentiviral lifecycle
We hypothesize that DNA damage response pathways, and the proteins involved in these pathways, play both pro- and anti-viral roles in the lentiviral lifecycle. This is a largely unexplored interface of lentiviral and host biology, and understanding the nature and relevance of engagement of the DNA damage response by lentiviruses will open the doors to identifying novel means of controlling HIV. We are focusing on reverse-transcription, nuclear import, and integration, as all of these steps are strong candidates to be regulated by the DNA damage response. In addition, we are interested in expanding our studies to understand how the DNA damage response can regulate latency of the integrated provirus by using various in vitro latent infection models. Latency is an important frontier in HIV cure research, and is of great interest as DNA damage response factors are involved in the regulation of chromatin dynamics that control latent proviral gene expression. |
Understand the function and evolution of lentiviral accessory genes
HIV-1 and other primate lentiviruses encode accessory proteins that enhance viral infectivity by either usurping host factors to facilitate their replication, or antagonizing antiviral factors. Currently, the lab is focusing on the accessory protein Vpr, with the overall goal of understanding its function in the lentiviral lifecycle and elucidating its mechanism(s) of action. Vpr is found in all extant primate lentiviruses, and many roles have been ascribed to it. Vpr has also been shown to be important for HIV and SIV pathogenesis in vivo. However, despite its persistence throughout primate lentiviral evolution and its importance in the viral lifecycle, the precise primary function of Vpr remains unclear. Therefore, we are working to unravel the complexity of Vpr by understanding the conservation (or lack thereof) of Vpr-host interactions and Vpr-associated phenotypes. |
Through these studies we hope to uncover novel aspects of lentiviral biology that can lead to enhanced measures in controlling HIV.