Description of Research Expertise

Research Interests: Understanding the immune and epigenetic relationship between host cells and viral pathogens using single-cell multiomic approaches

Keywords:HIV, immunology, viral and host epigenetics, gene expression modulation, mRNA gene therapy, single-cell genomics

Research Details:
The complex heterogeneity of human immunology and virally infected cells confounds the study of many infectious (i.e. HIV, EBV, HPV, and more) and associated oncological diseases. In many of these infections, latent viral infections persist and remain without a cure for multiple reasons including 1) sample rarity and sparsity of infected cells and 2) a heterogeneous pool of infected cells that requires single-cell methodology to decipher cellular phenotypes. As such, the Wu Lab uses a systems immunology approach to generate an unbiased, high-resolution, and multiomic assessment of valuable ex vivo samples. This approach combined with bioinformatics will identify, unlock, and evaluate targeted therapies against infected/aberrant cells from various disease contexts. As such, our long-term goal is to apply and develop single-cell approaches to find curative strategies for infectious and oncological diseases.

Our ongoing research directions include understanding how the HIV and SIV reservoirs change after therapeutic interventions or antiretroviral therapy interruption. Furthermore, we are actively exploring how proviral epigenetics are impacted by its host cell’s epigenetics using molecular biology approaches such as CUT&RUN. Another interest of the lab is the development of targeted DNA-specific strategies for chronic diseases, where we formulate mRNA-LNP strategies that encode transcription activator-like effector (TALEs) to modulate endogenous or viral genes in a specific manner. These research directions have multiple projects for graduate students who are interested in wet and/or dry lab.

Rotation Projects:
1) Development and adaptation of single cell profiling techniques to identify and phenotype the SIV/SHIV reservoir in non-human primate models.
2) Deciphering HIV proviral epigenetics at single-cell resolution during in vitro and ex vivo models of latency
3) Assessment of different epigenetic modifiers and activation domains in TALE-mediated latency reversal of HIV.
4) Assessment of TALE-mediated gene modulation delivered via mRNA-LNPs to address end stage liver disease.

Lab Personnel:
Sepideh Toshtzar - Research Technician