Ya-Chi Ho, MD, PhD

Despite effective antiretroviral therapy (ART), HIV persists in latently infected cells which is the major barrier to cure. Interruption in ART inevitably leads to viral rebound, and life-long ART is required for HIV-infected individuals. The goal of the Ho lab is to use molecular virology, T cell biology, genomics and single cell technology to understand mechanisms of HIV persistence and to develop HIV cure strategies. Using clinical samples from HIV-infected individuals, our translational approach may expedite the application of basic research into clinical uses.

Single-cell multi-omics understanding of HIV-induced immune dysfunction
The goal of the Ho lab is to exploit molecular virology, genetics, bioinformatics, immunology and single-cell technology to understand the mechanisms of HIV persistence and develop a cure for HIV. In particular, we use blood samples from HIV-infected individuals to interrogate HIV-host interactions ex vivo. Our translational approach bridges bench discoveries into clinical applications. Rotation projects are available from wet-bench virology/immunology experiments to computational and bioinformatic analyses on single-cell transcriptome, depending on the interest of the student.

HIV persistence in clonally expanding CD4+ T cells is the major barrier to cure. Studying HIV-infected cells in clinical samples has been challenging, due to the rarity, heterogeneity, and lack of cellular markers for HIV-infected cells. Using paired blood samples during viremia and after suppressive ART from a randomized and interventional clinical trial (Sabes study), we interrogated how immediate versus delayed ART affected HIV-induced immune dysfunction and HIV persistence. By capturing surface protein expression, cellular transcriptome, HIV RNA, and T cell receptor sequencing within the same single cells, we identified the clonal expansion dynamics of T cell clones harboring HIV and the transcriptional program driving HIV persistence and T cell proliferation.

Using genomics approach to understand mechanisms of HIV persistence and latency
HIV persists in the latent reservoir as the major barrier to cure. The size of the latent reservoir may increase through clonal expansion. Only 1-10 per million CD4+ T cells contain infectious HIV, and there is no reliable marker which can identify HIV-infected cells from HIV-infected patients for molecular characterization. We developed HIV SortSeq to identify HIV-infected cells from HIV-infected patients for single-cell RNAseq. We found that HIV promotes the survival of the infected cells through induction of aberrant transcription of cancer-related genes.