Ya-Chi Ho, MD, PhD
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Research Summary
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.
Extensive Research Description
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.
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Research Interests
Genetics; HIV; Immunotherapy; Microbiology; Host-Pathogen Interactions; Transcriptome; Epigenetic Repression
Public Health Interests
HIV/AIDS
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Selected Publications
- The single-cell landscape of immunological responses of CD4+ T cells in HIV versus severe acute respiratory syndrome coronavirus 2.Collora JA, Liu R, Albrecht K, Ho YC. The single-cell landscape of immunological responses of CD4+ T cells in HIV versus severe acute respiratory syndrome coronavirus 2. Current Opinion In HIV And AIDS 2021, 16: 36-47. PMID: 33165008, PMCID: PMC8162470, DOI: 10.1097/COH.0000000000000655.
- Filgotinib suppresses HIV-1-driven gene transcription by inhibiting HIV-1 splicing and T cell activation.Yeh YJ, Jenike KM, Calvi RM, Chiarella J, Hoh R, Deeks SG, Ho YC. Filgotinib suppresses HIV-1-driven gene transcription by inhibiting HIV-1 splicing and T cell activation. The Journal Of Clinical Investigation 2020, 130: 4969-4984. PMID: 32573496, PMCID: PMC7456222, DOI: 10.1172/JCI137371.
- Single-cell transcriptional landscapes reveal HIV-1-driven aberrant host gene transcription as a potential therapeutic target.Liu R, Yeh YJ, Varabyou A, Collora JA, Sherrill-Mix S, Talbot CC, Mehta S, Albrecht K, Hao H, Zhang H, Pollack RA, Beg SA, Calvi RM, Hu J, Durand CM, Ambinder RF, Hoh R, Deeks SG, Chiarella J, Spudich S, Douek DC, Bushman FD, Pertea M, Ho YC. Single-cell transcriptional landscapes reveal HIV-1-driven aberrant host gene transcription as a potential therapeutic target. Science Translational Medicine 2020, 12 PMID: 32404504, PMCID: PMC7453882, DOI: 10.1126/scitranslmed.aaz0802.
- SARS-CoV-2: a storm is raging.Pedersen SF, Ho YC. SARS-CoV-2: a storm is raging. The Journal Of Clinical Investigation 2020, 130: 2202-2205. PMID: 32217834, PMCID: PMC7190904, DOI: 10.1172/JCI137647.
- Defective HIV-1 Proviruses Are Expressed and Can Be Recognized by Cytotoxic T Lymphocytes, which Shape the Proviral Landscape.Pollack RA, Jones RB, Pertea M, Bruner KM, Martin AR, Thomas AS, Capoferri AA, Beg SA, Huang SH, Karandish S, Hao H, Halper-Stromberg E, Yong PC, Kovacs C, Benko E, Siliciano RF, Ho YC. Defective HIV-1 Proviruses Are Expressed and Can Be Recognized by Cytotoxic T Lymphocytes, which Shape the Proviral Landscape. Cell Host & Microbe 2017, 21: 494-506.e4. PMID: 28407485, PMCID: PMC5433942, DOI: 10.1016/j.chom.2017.03.008.
- Replication-competent noninduced proviruses in the latent reservoir increase barrier to HIV-1 cure.Ho YC, Shan L, Hosmane NN, Wang J, Laskey SB, Rosenbloom DI, Lai J, Blankson JN, Siliciano JD, Siliciano RF. Replication-competent noninduced proviruses in the latent reservoir increase barrier to HIV-1 cure. Cell 2013, 155: 540-51. PMID: 24243014, PMCID: PMC3896327, DOI: 10.1016/j.cell.2013.09.020.
Clinical Trials
Conditions | Study Title |
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Diseases of the Nervous System; HIV/AIDS; Infectious Diseases; COVID-19 Inpatient; COVID-19 Outpatient | HIV Associated Reservoirs and Comorbidities (The HARC Plus Study) |
HIV/AIDS | Evaluating the role of opioid medication assisted therapies in HIV-1 Persistence |
HIV/AIDS | Mechanisms of HIV latency |