Our research is based on two main pillars: Firstly, we develop new tools to characterize viral reservoirs and provide diagnostic assays that can be used in HIV Cure studies. Secondly, we perform basic research on HIV latency and pathogenesis, hereby focusing largely on long non-coding RNAs.
Characterization of the HIV reservoir in vivo
We develop and use new sensitive techniques to investigate the size and dynamics of the HIV reservoir in HIV patients. We have ongoing projects investigating the impact of specific antiretroviral regimens on the size of the HIV reservoir, but also projects including elite controllers and functional cured patients. These comprise of a small group of patients that are able to suppress HIV disease progression without requiring antiretroviral therapy.
We recently developed state of the art sensitive quantification tools to measure total and episomal HIV DNA (2LTR circles) and cellular HIV RNA using the droplet digital PCR platform (ddPCR). In addition, we perform a more generic variant of digital PCR to exclusively quantify the amount integrated HIV DNA which was recently published.
We are now focusing on integration site sequencing of proviral HIV DNA and analyzing the methylation profile of integrated proviruses.
Using these tools we have started and are collaborating in several clinical studies.
Investigation of long non-coding RNAs in HIV disease/latency
Long non-coding RNAs (lncRNAs) have long been neglected as bulk RNA with no biological function. However, it is now becoming increasingly clear that these molecules actually play various and important roles in cellular pathways, including transcriptional regulation and epigenetic editing. Because of the importance of transcription and epigenetic mechanisms in HIV latency, our group started to investigate these molecules in HIV infection and in HIV latency establishment using an in vitro HIV latency model. We perform transcriptome profiling to discover key lncRNAs in HIV infection and latency using mircroarray, deep sequencing and specific RT-qPCR. In addition, we perform in vitro lncRNA knock down experiments to experimentally falsify the functional role of these molecules.