Ya-Chi Ho, MD, PhD, MMS

Assistant Professor of Microbial Pathogenesis and Medicine (Infectious Diseases); Investigator, HIV Reservoirs and Viral Eradication Transformative Science Group (Cure TSG)

Research Departments & Organizations

Microbial Pathogenesis: Ya-Chi Ho Lab

Center for RNA Science and Medicine

Internal Medicine

Virology Laboratories

Yale Cancer Center: Virus and Other Infection-associated Cancers

Research Interests

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

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

The Ho lab is using molecular, genomic, bioinformatic and translational approaches to examine host-pathogen interactions and develop novel HIV cure strategies.

1) "One HIV at a time" - HIV proviral and viral landscape: HIV proviral landscape is dynamic due to differential immune selection (Cell Host Microbe 2017, selected as the Best of Cell Host Microbe 2017) and clonal expansion of specific subtypes of HIV proviruses. We examine HIV proviral landscape using single genome HIV proviral sequencing and HIV RNA landscape using HIV SortSeq (R01).

2) "HIV-1-host interactions": Using single-cell RNAseq and CRISPR-Cas9-based methods, we study HIV-host chromatin interactions and HIV mediated aberrant host gene transcription in cell line models and in clinical samples.

3) "The block-and-lock" - HIV epigenetic silencing: We have previously found that HIV proviruses are not CpG methylated in the promoter in clinical samples (Cell 2013, cover story). HIV reactivation is stochastic, making it challenging to reactivate all HIV-infected cells for immune clearance. We are exploring methods to silence HIV expression for a long-term HIV remission or "functional cure", using a CRISPR-based cellular factor screen and a small compound library screen.

4) "HIV immune evasion using decoys" - defective HIV proviruses as the cause of chronic immune activation or as a strategy for therapeutic vaccine development: We have previously found that a specific type of defective HIV proviruses, the "hypermutated" ones which containing premature stop codons throughout the genome, may induce immune recognition. We are exploring whether these defective HIV proviruses cause immune activation, or if they can be used as therapeutic vaccines to boost the immune response.

Clinical Trials

Conditions Study Title
HIV/AIDS Evaluating the role of opioid medication assisted therapies in HIV-1 Persistence
HIV/AIDS Mechanisms of HIV latency

Activities

  • Oral presentation, Keystone Symposia: Functional Cures and the Eradication of HIV (X8) Whistler, Canada (2019 - 2019)

  • Invited Speaker, Conferences on Retroviruses and Opportunistic Infections (CROI) Seattle, United States (2019 - 2019)

  • Invited Speaker, Conferences on Retroviruses and Opportunistic Infections (CROI) Seattle, United States (2019 - 2019)

  • Invited Speaker, NIH Strategies for an HIV Cure Bethesda, United States (2018 - 2018)

  • Invited Speaker, NIH Strategies for an HIV Cure Bethesda, United States (2018 - 2018)

  • Invited Speaker, Academic Research Faculty Careers Workshop, Johns Hopkins University School of Medicine Baltimore, United States (2018 - 2018)

  • Invited Speaker, Academic Research Faculty Career Workshop, Johns Hopkins University School of Medicine Baltimore, United States (2018 - 2018)

  • Invited Speaker and session co-chair, AIDS 2018, The International AIDS Meeting Amsterdam, Netherlands (2018)

  • Invited Speaker, AACR Special Conference on Cancer: Dormancy and Residual Disease Montreal, Canada (2018 - 2018)

  • Invited Speaker, University of Washington/Fred Hutchinson Center for AIDS Research Seminar Seattle, United States (2018 - 2018)

  • Invited Speaker, Keystone Symposia, HIV and Co-Infections Whistler, Canada (2018 - 2018)

  • Oral presentation, Conference on Retroviruses and Opportunistic Infections (CROI) Boston, United States (2018 - 2018)

  • Oral presentation, HIV Persistence During Therapy Workshop Miami, United States (2017 - 2017)

  • Invited Speaker, The International Meeting of the Institute of Human Virology Baltimore, United States (2017 - 2017)

  • Invited Speaker, Conference on Cell & Gene Therapy for HIV Cure Seattle, United States (2017 - 2017)

  • Invited Speaker, The Department of Microbiology, Immunology, and Tropical Medicine Seminar Washington, United States (2015 - 2015)

Selected Publications

See list of PubMed publications

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Contact Info

Ya-Chi Ho, MD, PhD, MMS
Lab Location
Ya-Chi Ho LabBoyer Center for Molecular Medicine
295 Congress Avenue, Rm BCMM 349

New Haven, CT 06510
Office Location
Boyer Center for Molecular Medicine
295 Congress Avenue, Rm BCMM 354E

New Haven, CT 06510

Curriculum Vitae

Ya-Chi Ho Lab