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Ho Lab News

2021/3/23 Our Commentary "Shock-and-kill versus block-and-lock: Targeting the fluctuating and heterogeneous HIV-1 gene expression" is now published at PNAS

We published our Commentary on druggable pathways for the shock-and-kill versus block-and-lock strategies for HIV eradication.
First published on March 23, 2021: https://www.pnas.org/content/118/16/e2103692118
Commenting on: https://www.pnas.org/content/118/11/e2012191118

Thanks to our postdoc Jimmy nicely summarized the strategies for identifying drugs and cellular pathways for HIV eradication!

2021/1/29 We are recruiting a postdoc working on HIV + single-cell genomics + bioinformatics! Join us!

2021/1/28 Jack's manuscript on single-cell multi-omic profiling of HIV-infected cells is now posted on bioRxiv!

Jack's manuscript entitled "Single-cell immune profiling reveals the impact of antiretroviral therapy on HIV-1-induced immune dysfunction, T cell clonal expansion, and HIV-1 persistence in vivo" is now posted on bioRxiv and under peer review in a journal!

https://www.biorxiv.org/content/10.1101/2021.01.27.428491v1.full.pdf

2021/1/27 Yale first year undergrad student Kerui joined the lab!

Yale first year student Kerui Yang joined our lab to work on cellular factors critical for HIV-1 expression. As a freshman, Kerui came with 5 years of research experience and strong interest in HIV. Welcome Kerui!

2021/1/15 Jack received New Investigator Scholarship from Conference on Retroviruses and Opportunistic Infections (CROI) and will present his work as a Scientific Spotlight

Jack received the New Investigator Scholarship for the prestigious meeting CROI for his abstract entitled "Cytokine dysregulation and antigen responses drive T cell clonal expansion in HIV infection". He will present his work as a Scientific Spotlight at CROI 2021. Congrats Jack!

2021/1/11 Yale MPH student Allie joined the lab!

Yale MPH student Allison Catalano joined our lab to work on HIV persistence. Allie brings in her clinical insight as an Infection Control Practitioner to HIV persistence and translational research. Welcome Allie!

2020/11/11 Our review "The single-cell landscape of immunological responses of CD4+ T cells in HIV versus SARS-CoV-2" is published at Current Opinion in HIV and AIDS

Our lab runs weekly single-cell meetings in addition to weekly lab meetings to keep updated on single-cell applications to important biological questions. During COVID-19, we extended our interest in HIV-induced immune dysfunction to SARS-CoV-2-induced immune dysfunction and updated single-cell advances in COVID-19, from preprints to epub-ahead-of-print papers. Here, our PhD students (Jack and Kristen) and postdoc (Runxia) compared virus-induced immune dysfunction in HIV versus SARS-CoV-2, focusing on single-cell understanding of CD4+ T cell biology in these two important viral infections. Epub ahead of print at Current Opinion in HIV and AIDS.

https://journals.lww.com/co-hivandaids/toc/publishahead

2020/11/4 Yale Bridging the Gap Fund helps labs to maintain scientific productivity under COVID-19

Our lab received the Bridging the Gap Fund from the Dean of Yale School of Medicine and the Chair of Department of Microbial Pathogenesis to ensure scientific advancement during this difficult time. Our Yale colleagues from Dr. Iwasakis' lab and Dr. Wilen's lab provided generous help for COVID-19 research. Yale EHS provided comprehensive protection procedures to keep researchers safe and productive both at BSL3 and on campus. We are fortunate and grateful to continue our fight against formidable infectious diseases, namely HIV and SARS-CoV-2. Here our postdoc Runxia and PhD student Jack extended our love fighting against HIV toward COVID-19.

Thanks to Yale, our lab maintains near-normal capacity in a safe environment with abundant PPE provided by Yale EHS.

2020/7/29 Postdoc Runxia Liu received 2020 Immune Profiling Award from 10x Genomics

Congratulations to Runxia for receiving the 2020 Immune Profiling Award from 10x Genomics for single-cell multi-omics profiling!

2020/6/23 Our article using drug screen and transcriptome analysis on mechanisms of HIV-suppressing agents by Jimmy is published at Journal of Clinical Investigation!

"Filgotinib suppresses HIV-1-driven gene transcription by inhibiting HIV-1 splicing and T cell activation"

Despite effective antiretroviral therapy, HIV-1-nfected cells continue to produce viral antigens and induce chronic immune exhaustion. We propose to identify HIV-1-suppressing agents which can inhibit HIV-1 reactivation and reduce HIV-1-induced immune activation. Using a novel dual reporter system and a high-throughput drug screen, we identified FDA-approved drugs which can suppress HIV-1 reactivation in both cell line models and CD4+ T cells from virally suppressed, HIV-1-infected individuals. We identified 11 cellular pathways required for HIV-1 reactivation as druggable targets. Using differential expression analysis, gene set enrichment analysis and exon-intron landscape analysis, we examined the impact of drug treatment on the cellular environment at a genome-wide level. We identified a new function of a JAK inhibitor filgotinib which suppresses HIV-1 splicing. First, filgotinib preferentially suppresses spliced HIV-1 RNA transcription. Second, filgotinib suppresses HIV-1-driven aberrant cancer-related gene expression at the integration site. Third, we found that filgotinib suppresses HIV-1 transcription by inhibiting T cell activation and by modulating RNA splicing. Finally, we found that filgotinib treatment reduces the proliferation of HIV-1-infected cells. Overall, the combination of a drug screen and transcriptome analysis provides systemic understanding of cellular targets required for HIV-1 reactivation and drug candidates that may reduce HIV-1-related immune activation.

This work is led by our talented postdoc Jimmy who has no prior research experience in HIV or bioinformatics. He completed both wet-bench HIV experiments from blood samples and all bioinformatic analysis from scratch, along with the other Science Translational Medicine paper in which he was a co-first author, within 2 years and 8 months after joining our lab. He has presented this work as 2 talks, 3 posters, and 2 travel grants in extramural/international meetings. Congrats Jimmy!

2020/5/13 Our article using HIV-1 SortSeq to characterize single-cell transcriptional landscape by Runxia and Jimmy is published at Science Translational Medicine

We developed HIV-1 SortSeq which captures the rare HIV-1-infected cells for single-cell RNAseq.

"Single-cell transcriptional landscapes reveal HIV-1–driven aberrant host gene transcription as a potential therapeutic target"
Science Translational Medicine 13 May 2020: Vol. 12, Issue 543, eaaz0802; DOI: 10.1126/scitranslmed.aaz0802
https://stm.sciencemag.org/content/12/543/eaaz0802/
Video abstract: https://youtu.be/QGnn6IspsrA
News report: https://news.yale.edu/2020/05/13/yale-researchers-discover-how-hiv-hides-treatment

We are proud to present our work, from single-cell HIV capture, CRISPR-mediated HIV-1 perturbation to single-cell transcriptome analysis, published within three years starting our lab. This is the team work from our postdocs and students who are relatively junior in the HIV field (<3 years). First authors: our postdocs Runxla Liu (HIV-1 SortSeq) and Yang-Hui Jimmy Yeh (HIV-1-driven aberrant cancer gene expression landscape) and Johns Hopkins PhD student Ales Varabyou (HIV-host chimeric RNA bioinformatic capture), with help from our PhD student Jack Collora (single-cell transcriptome analysis and CRISPRa/i system) and Kristen Albrecht (HIV-1 gRNA construction). This work is made possible by generous support from our study participants and our collaborators at Yale, Johns Hopkins University, UPenn, UCSF, and NIH as well as funding from Yale, NIH, and Gilead HIV Research Scholar Grant.

2020/5/13 Ho Lab is presenting three talk at the Cold Spring Harbor Laboratory Meetings on Retroviruses, May 18-21, 2020

We are sharing our work as three talks at the CSHL Meetings on Retroviruses:

2020/5/20, 10 am, Jack: Single-cell atlas and clonal expansion dynamics of CD4+ T cells during HIV-1 infection
2020/5/20, 10am, Ya-Chi:Single-cell transcriptional landscape reveals HIV-1-driven aberrant host gene transcription as a therapeutic target
2020//5/21, 2 pm, Jimmy: A combination of drug screen and RNA landscape reveals targetable pathways in HIV-1 reactivation

Ya-Chi will be available at the "Meet the Speakers (MtS) Session" at 5:30 pm, Wednesday, May 20 and 5:30pm, Thursday, May 21.
See you all on SLACK and ZOOM!

2020/5/1 Our Commentary "SARS-CoV-2: a storm is raging" is now published at Journal of Clinical Investigation

We published our Commentary on SARS-CoV-2-induced cytokine storms at the Journal of Clinical Investigation, focusing on how SARS-CoV-2 induces cytokine storms and leads to mortality.
First published on March 27, 2020: https://www.jci.org/articles/view/137647
Commenting on: https://www.jci.org/articles/view/137244
Interviewed at the Wall Street Journal, April 9, 2020: https://www.wsj.com/articles/haywire-immune-response-eyed-in-coronavirus-deaths-treatment-11586430001

Thanks to our postgrad Savannah who nicely summarized the rapidly evolving updated research findings and provided an insightful mini-review on COVID19.

2020/4/15 Darla is admitted to the Cellular and Molecular Medicine PhD program at Johns Hopkins University School of Medicine!

Congratulations to our NIH-PREP postgrad student Darla who is accepted to the Cellular and Molecular Medicine Program at Johns Hopkins University School of Medicine - where Dr. Ho received her PhD degree too! Way to go Darla!

2020/3/31 Darla received Honorable Mention on NSF Graduate Research Fellowship Program (GRFP)!

Darla's proposal working on HIV RNA-protein interactions received Honorable Mention for the NSF Graduate Research Fellowship Program! Photo showing a part of her project presented at the Yale Micro Retreat 2019. Big congrats, Darla!

2020/2/7 American Foundation for AIDS Research (amfAR) grant supporting our single-cell work

In collaboration with our amazing Yale computer scientist David van Dijk, we got an amfAR Magnet Grant together entitled "The driving force of the clonally expanding HIV-1-infected cells - a single-cell approach", based on the hard work by our student Jack. It's a great pleasure to join the fight against HIV with amfAR!

2020/1/31 Kristen is now a PhD candidate!

Congratulations to our PhD student, Kristen Albrecht, Yale BBS Microbiology track, who passed PhD oral qualification today with an truly nicely written proposal!
Many thanks to distinguished thesis committee members: Joe Craft, Rong Fan and Walther Mothes.

2020/1/7 Our review article "The forces driving clonal expansion of the HIV-1 latent reservoir" is now published!

How do HIV-1-infected cells undergo clonal expansion?
Does HIV-1 integration site matter?
A complicated battle between antigen stimulation, homeostatic proliferation and HIV-1 insertional mutagenesis is reviewed here.

Congrats to our postdoc Runxia and our wonderful collaborator Francesco Simonetti!

Inspired by Nicolas Gillet/Charles Bangham, Blood 2011
Frank Maldarelli/Steve Hughes, Science 2014
Thor Wagner/Lisa Frenkel, Science 2014
Francesco Simonetti/Frank Maldarelli, PNAS 2016
Zheng Wang/Robert Siliciano, PNAS 2018
Chrisopher Nobels/Rick Bushman, JCI 2019
Liu/Yeh/Varabyou/Collora/Ho, HIV-1 SortSeq, in revision

https://virologyj.biomedcentral.com/articles/10.1186/s12985-019-1276-8

2019/11/14 Jack and Jimmy received New Investigator Award!

Jack received New Investigator Scholarship for his work "Single-cell atlas and clonal expansion dynamics of CD4+ T cells during HIV infection" as a themed discussion (oral and poster presentation) at CROI 2020.

Jimmy received New Investigator Scholarship for his work "A Jak1 inhibitor suppresses HIV-1-driven aberrant host gene transcription" as a poster presentation at CROI 2020.
Congratulations to two New Investigators!


2019/4/9 Jack received Honorable Mention on NSF Graduate Research Fellowship Program (GRFP)!

Jack's proposal entitled "Functional 3D genome architecture dynamics as a mechanism of retroviral persistence" received Honorable Mention for the NSF Graduate Research Fellowship Program! Photo showing a part of his project presented at the Yale Micro Retreat 2019, which was also previously presented at the Nature Conference Next-Generation Genomics at New York Genomics Center on August 12, 2019. Big congrats, Jack!

2019/5/10 Yale BBS Microbiology track PhD student Kristen joined the lab!

Kristen started her rotation on 2018/9/4. She brought in extensive experience in molecular biology and virology research at Dr. Lynn Enquist's lab at Princeton University. She will explore different cutting-edge technologies to study HIV-1 persistence.

2019/4/25 Dr. Ho served as the extramural member of Radwa Sharaf's PhD thesis defense committee at Harvard Virology

Dr. Ho served as the thesis defense committee member for (now Dr.) Radwa Sharaf at Harvard Virology PhD program. Congrats to Radwa and her mentors, Dr. Jonathan Li and Dr. Daniel Kuritzkes, for the excellent research and presentation!

2019/4/19 Savannah presented her senior thesis at the Yale MCDB Poster Symposium!

Savannah presented her outstanding senior thesis at the Yale MCDB Poster Symposium. Mentored by PhD student Jack, Savannah conducted molecular cloning and a CRISPR screen within one year. Great work, Savannah!

2019/4/4 Jack is now a PhD candidate!

Congratulations to our PhD student, Jack Collora, Yale BBS Microbiology track, who passed PhD oral qualification today. Truly exceptional work!
Many thanks to distinguished thesis committee members: Walther Mothes, Craig Wilen, Matthew Simon.

2019/3/6 Ya-Chi gave an invited talk at CROI 2019

Ya-Chi gave an invited talk at CROI 2019 entitled "The power of the HIV promoter, impact of HIV-driven viral and host gene expression". Very excited to witness history - in this meeting where the second HIV cure, "The London Patient", was announced!!

2019/3/1 Ryan is accepted to University of Washington Microbiology PhD program!

Congratulations to our Master's student Ryan who is accepted to University of Washington Microbiology PhD program! So glad that he is continuing to make discoveries in HIV research!

2018/12/1 Postgrad Samana joined the lab!

Postgrad Samana Zaidi joined our workforce toward understanding HIV and curing HIV infection, bringing in her extensive experience in clinical sample processing and molecular biology. Welcome Samana!

2018/9/17 Jimmy, Runxia and Jack received BEAT-HIV Delaney Collaboratory Travel Awards to present their work at the NIH Strategies for an HIV Cure Meeting!

Congrats to Postdoc Jimmy, postdoc Runxia and PhD student Jack who received Travel Awards from the BEAT-HIV Delaney Collaboratory to present their posters at the NIH Strategies for an HIV Cure Meeting. Dr. Ho will give an invited talk. Great work, Jimmy, Runxia and Jack!

2018/8/31 Dr. Ho was awarded a second NIH funding R61/R33 (R01 equivalent) to investigate the chromatin environment of HIV-1-infected cells (within one year after she started the lab).

R61/R33 title: "Evaluating the role of opioid medication assisted therapies in HIV-1 Persistence for persons living with HIV and opioid use disorders". PI: Sandra Springer. Co-PI: Ya-Chi Ho and Yuval Kluger.

2018/8/25 Dr. Ho's paper was selected as 1 of the 8 "Best of Cell Host Microbe 2017".

Dr. Ho's paper entitled "Defective HIV-1 Proviruses Are Expressed and Can Be Recognized by Cytotoxic T Lymphocytes, which Shape the Proviral Landscape" is selected as the Best paper of Cell Host Microbe!

2018/8/17 Dr. Ho is awarded a NIAID/NIH R01 grant (within one year after she started the lab).

R01 title: "Role of clonal expansion in HIV-1 persistence". PI: Ya-Chi Ho.

2018/7/25 Dr. Ho gave an invited talk and chaired a session at the International AIDS Society Annual Meeting (AIDS), Amsterdam, Netherlands

Presented in session: "Eliminating HIV latency: Shock and kill or block and lock?"
Chaired session: "Poking, prodding and purging the final reservoir frontier"

2018/7/13 Yale MCDB senior Savannah Pedersen joined the lab for her senior thesis. Welcome Savannah!

Savannah has a strong passion toward understanding and treatment of human diseases. She will develop a model to study HIV-1 persistence.

2018/6/21 Dr. Ho gave an invited talk at the American Association for Cancer Research (AACR) special meeting on Cancer Dormancy and Residual Disease

Talk title: "Targeting the one in a million: Detection and elimination of the HIV latent reservoir"

2018/6/19 PhD Student Jack will present a poster at Yale HIV Symposium

PhD student Jack's abstract on HIV interactions with the human genome is accepted to the Yale HIV Symposium within 3 months after he joined. Well done Jack!

2018/6/7 Dr. Ho gave an invited talk at the Center for AIDS Research (CFAR) at the University of Washington at Seattle/Fred Hutchinson Cancer Center

Talk title: "HIV-1 RNA SortSeq: HIV-1 driven aberrant host gene expression contributes to HIV-1 persistence"

2018/5/24 Dr. Ho was one of the 4 panelists hosting the HIV Cure Colloquium at the Cold Spring Harbor Retroviruses Meeting

2018/5/22 This Week in Virology (TWiV) recording
2018/5/23 Andy Kaplan Prize talk
2018/5/24 HIV Cure Colloquium

2018/4/19 Dr. Ho gave an invited talk at the Keystone Symposia: HIV and Co-Infections: Pathogenesis, Inflammation and Persistence (X8)

Talk title: "HIV-1 Viral and Proviral Landscape"

2018/4/18 Postdoc Runxia Liu will present a poster at the Cold Spring Harbor Laboratory Meetings on Retroviruses at Cold Spring Harbor, NY.

Runxia's abstract on HIV-1 splicing is accepted to Cold Spring Harbor Meetings on Retroviruses, within 3 months after she joined the lab. Well done, Runxia!

2018/4/5 Dr. Ho received the Andy Kaplan Prize, Cold Spring Harbor Laboratory Meetings in Retroviruses.

The goal of the Andy Kaplan Prize is to advance the career and honor the accomplishments of one distinguished postdoctoral scientist each year as he/she embarks on an independent career in retrovirology.

2018/3/27 Yale BBS Microbiology track PhD student Jack joined the lab!

Jack started his rotation on 2018/2/8. He gained his expertise in lentiviral tranduction, primary cell models and molecular biology in Donald Kohn's lab at UCLA. As a Gruber fellow, he will apply multidisciplinary research, including chromatin conformation analysis, bioinformatics, immunology, T cell biology and HIV virology, to understand HIV persistence.

2018/3/19 Dr. Ho received Gilead Sciences Research Scholars Award in HIV.

"Gilead Sciences Research Scholars Program in HIV (the "program") is to support innovative scientific research that will advance knowledge in the field of HIV and provide support for research career development.". This research grant is award to 4 HIV investigators each year.

2018/3/7 Dr. Ho gave a talk at the Conferences on Retroviruses and Opportunistic Infections (CROI), Boston.

Talk title: "Identification of integration sites of inducible HIV-1 using HIV-1 RNA SortSeq"

2018/1/31 Postdoc Jimmy Yeh will present a poster at the Keystone Symposia: HIV and Co-Infections: Pathogenesis, Inflammation and Persistence (X8) at Whistler, Canada.

Jimmy's abstract on HIV-1 silencing agents was accepted to Keystone Symposia within 3 months after he joined the lab. Well done, Jimmy!

2018/1/22 Postdoc Runxia Liu joined the lab!

Runxia worked on the pathogenesis of influenza virus during her PhD training. Specifically, she has been studying how defective influenza virus may affect infection in vivo. Her expertise in splicing and virology brings novel insights into the HIV pathogenesis.

2018/1/3 The Ho Lab received the Endowed Anderson Postdoctoral Fellowship.

This fellowship supports the stipend for a postdoc fellow for one year.

2018/12/13 Dr. Ho gave a talk at the HIV Persistence During Therapy Meeting, Miami

Talk title: "HIV-1 proviruses which are integrated into cancer-related genes are inducible"

2017/12/6 Dr. Ho was selected as the Yale Top Scholar - Lois E. and Franklin H. Top, Jr. Yale Scholar, Yale University School of Medicine, 2017-2021.

The Top Scholar Award kindly supports the establishment of a successful lab.

2017/11/16 Postdoc Yang-Hui (Jimmy) Yeh joined the lab!

Jimmy's developed a broad knowledge in molecular biology during his PhD training and virology during his postdoc training. He is developing bioinformatics and pharmacologic methods to find HIV-1 silencing agents as a novel HIV-1 treatment strategy.

2017/9/1 The Ho Lab started!

The goal of the Ho lab is to understand HIV persistence and find a cure for HIV-1 infections. The Ho lab uses multidisciplinary approaches on T cell biology, transcriptomics, genomics, virology and pharmacology with particular focus human samples. The translation approach may provide insights into immediate clinical applications.