Vincent Wu, Ph.D.

We have pioneered the use of single-cell techniques (viral scASAPseq and scDOGMAseq) that take advantage of epigenetic readouts such as scATACseq to recover integrated HIV DNA, thereby marking the cells as infected during in silico analysis. Our studies from peripheral blood and lymphoid tissue documented the immense heterogeneity of HIV infected cells and established the use of these techniques to better understand the dynamic changes after therapeutic interventions or antiretroviral therapy interruption.

Recent work from us and from the field have highlighted the epigenetic complexity at the HIV proviral locus. Given our finding of infected cell heterogeneity, we are actively exploring how the epigenetics by the HIV provirus are impacted by its host cell’s epigenetics using molecular biology approaches such as CUT&RUN. A better understanding of this relationship is critical in our efforts to address HIV latency.

In collaboration with the Institute of RNA Innovation at the University of Pennsylvania, we have recently developed mRNA-LNP strategies that encode transcription activator-like effector (TALEs) to address various chronic diseases, including HIV latency reversal and liver associated diseases. By fusing various proteins, we are able to use the TALEs as a tethering platform to modulate endogenous or viral genes in a targeted and specific manner. The continued development of this platform as well as exploration of other DNA-specific recognition proteins (such as CRISPR) is ongoing.