Ya-Chi Ho, MD, PhD

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.