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Ya-Chi Ho, MD, PhD

Associate Professor Term
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Additional Titles

Director of Graduate Studies, Microbiology PhD Program of Biological and Biomedical Sciences

About

Titles

Associate Professor Term

Director of Graduate Studies, Microbiology PhD Program of Biological and Biomedical Sciences

Biography

Dr. Ho's research program focuses on understanding HIV-1 persistence and HIV-1-induced immune dysfunction using single-genome and single-cell approaches on clinical samples. She received MD in 2002 (Phi Tau Phi) and completed internal medicine residency and infectious disease fellowship training in Taiwan in 2007. She practiced as an infectious disease attending physician for one year (2007-2008). She received PhD at Johns Hopkins University School of Medicine (Phi Beta Kappa, HHMI International Student Research Fellowship, and Johns Hopkins Young Investigator Award) in 2013, mentored by Dr. Robert F. Siliciano. During PhD, she developed the first HIV-1 full-length single-genome sequencing method that became the standard measurement of the size of the HIV-1 latent reservoir (Cell 2013). As a postdoc, she profiled HIV-1 DNA and RNA landscape and identified the impact of cytotoxic T lymphocytes (CTLs) and defective HIV-1 proviruses on HIV-1 persistence (Cell Host Microbe 2017, Best Paper of the Year, corresponding author).

After she started my lab at Yale University in September 2017, she developed single-cell HIV-1 SortSeq and identified HIV-1-driven aberrant cancer gene expression at the integration site as a mechanism of HIV-1 persistence (Science Translational Medicine 2020).She developed CRISPR-ready HIV-1-infected cell-line models and a dual-reporter drug screen to identify drugs that can suppress HIV-1-induced cancer gene expression (JCI 2020). She is currently working on understanding HIV-1-induced immune dysfunction and clonal expansion dynamics of HIV-1-infected cells using single-cell multi-omic ECCITEseq on clinical samples (Immunity 2022). She found that HIV-1 preferentially persist in cytotoxic CD4+ T cells. She also found that antigen stimulation and tumor necrosis factor (TNF) as key drivers for the clonal expansion of HIV-1-infected cells. This is the first time identifying single-cell transcriptional landscape of HIV-1 RNA+ cells at their in vivo state without ex vivo stimulations. In addition, she used a genomewide CRISPR screen and identified HIV-1 silencing factors including SAFB family proteins and RNA nuclear exosome complex (J Virol 2022).

Dr. Ho's research support mainly comes from NIH, with an R21 funded 1 year after PhD graduation and two R01-level grants funded within one year after she started her lab at Yale University. She is focusing on using single-cell genomic approaches to understand HIV-1 persistence. She is an Investigator for basic science and translational collaboration projects, such as NIH Structural Biology Center CHEETAH, NIH Martin Delaney Collaboratory BEAT HIV and REACH, a UM1, and a P01.

Appointments

Education & Training

Postdoctoral fellow
Johns Hopkins School of Medicine (2014)
PhD
Johns Hopkins University School of Medicine, Cellular and Molecular Medicine (2013)
MMS
National Taiwan University, Clinical Medicine (2007)
Clinical fellow
National Taiwan University Hospital (2007)
Resident
National Taiwan University Hospital (2005)
MD
National Cheng Kung University, Medicine (2002)

Research

Overview

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.

Medical Subject Headings (MeSH)

Epigenetic Repression; Genetics; HIV; Host-Pathogen Interactions; Immunotherapy; Microbiology; Transcriptome

Research at a Glance

Yale Co-Authors

Frequent collaborators of Ya-Chi Ho's published research.

Publications

Featured Publications

2024

2023

2022

Clinical Trials

Current Trials

Academic Achievements & Community Involvement

  • activity

    Single-Cell Multiomics Reveals Persistence of HIV-1 in Expanded Cytotoxic T cell Clones

  • honor

    Andy Kaplan Prize

  • honor

    Gilead Sciences Research Scholar in HIV

  • honor

    Rudolf J. Anderson Fellowship

  • honor

    Lois E. and Franklin H. Top, Jr. Yale Scholar

Get In Touch

Contacts

Locations

  • Boyer Center for Molecular Medicine

    Academic Office

    295 Congress Avenue, Rm BCMM 354E

    New Haven, CT 06510

  • Ya-Chi Ho Lab

    Lab

    Boyer Center for Molecular Medicine

    295 Congress Avenue, Rm BCMM 349

    New Haven, CT 06510