Hongyan Guo, PhD
Assistant Professor of Microbiology and Immunology
Bachelor of Science, Biotechnology, Nankai University, China
PhD, Molecular Virology, Nankai University, China
Post-Doctoral Fellowships: Emory University (2013-2015), University of Texas Health Science Center at San Antonio (UTHSCSA, 2015-2017), and Georgia State University (2018-2021)
Research
Herpesviruses are among the most widespread human pathogens and are well known for their ability to establish lifelong infections. They have evolved diverse strategies to manipulate the host immune system to persist within the host. A major focus of our laboratory is investigating how innate immune signaling influences herpesvirus infection and pathogenesis, with particular emphasis on the role of regulated cell death pathways—such as necroptosis—in host defense. These pathways are critical for eliminating infected cells, thereby serving as a frontline defense against viral infection.
Our research primarily centers on the pathogenesis of Herpes Simplex Virus (HSV). The long-term goal of our work is to elucidate how disruptions in immune sensing, signaling, and gene regulation contribute to infectious, inflammatory, and autoimmune diseases. By integrating approaches from genetics, molecular and cell biology, virology, and immunology, we aim to unravel these complex signaling networks and ultimately enhance the diagnosis and treatment of human diseases.
Project 1: The Role of Cell Death in HSV-1 Pathogenesis
Receptor-interacting protein kinase 3 (RIPK3) is a central regulator of programmed cell death, activated by upstream molecules such as RIPK1, TRIF, and ZBP1. ZBP1 acts as an intracellular sensor of Z-form nucleic acids and recruits RIPK3 to initiate cell death. Our research focuses on the ZBP1 ligands that activate ZBP1, elucidating the mechanisms of ZBP1 activation, and determining the downstream effects of this pathway during HSV-1 infection and pathogenesis. These studies aim to define ZBP1’s role as a key antiviral sensor and uncover how HSV-1 subverts host cell death pathways to facilitate infection.
Project 2: Targeting Necroptosis Pathways in Tumors using Oncolytic HSV-1
Oncolytic virotherapy is a promising cancer treatment strategy that employs viruses to selectively infect and destroy tumor cells while sparing normal tissue. HSV-1 is particularly well-suited for this approach due to its broad cellular tropism and amenability to genetic engineering. Our research explores how engineered HSV-1 can be used to induce necroptosis—a form of regulated cell death—in cancer cells, thereby enhancing antitumor immune responses. By leveraging synergistic tumor models, we aim to dissect the role of necroptosis in oncolytic virus therapy and contribute to the development of safer, more effective, and highly targeted cancer treatments.
News
Publications
Selected Publications [† co-senior authors; * co-first authors]
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Amusan OT, Wang S, Yin C, Koehler HS, Li Y, Tenev T, Wilson R, Bellenie B, Zhang T, Wang J, Liu C, Seong K, Poorbaghi SL, Yates J, Shen Y, Upton JW, Meier P, Balachandran S, Guo H. RIPK1 is required for ZBP1-driven necroptosis in human cells. PLoS Biol. 2025 Feb 21;23(2):e3002845. doi: 10.1371/journal.pbio.3002845. PMID: 39982916; PMCID: PMC11844899.
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Mannion J, Gifford V, Bellenie B, Fernando W, Ramos Garcia L, Wilson R, John SW, Udainiya S, Patin EC, Tiu C, Smith A, Goicoechea M, Craxton A, Moraes de Vasconcelos N, Guppy N, Cheung KJ, Cundy NJ, Pierrat O, Brennan A, Roumeliotis TI, Benstead-Hume G, Alexander J, Muirhead G, Layzell S, Lyu W, Roulstone V, Allen M, Baldock H, Legrand A, Gabel F, Serrano-Aparicio N, Starling C, Guo H, Upton J, Gyrd-Hansen M, MacFarlane M, Seddon B, Raynaud F, Roxanis I, Harrington K, Haider S, Choudhary JS, Hoelder S, Tenev T, Meier P. A RIPK1-specific PROTAC degrader achieves potent antitumor activity by enhancing immunogenic cell death. Immunity. 2024 Jul 9;57(7):1514-1532.e15. doi: 10.1016/j.immuni.2024.04.025. Epub 2024 May 23. PMID: 38788712; PMCID: PMC11236506.
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Newton K, Wickliffe KE, Maltzman A, Dugger DL, Webster JD, Guo H, Dixit VM. Caspase cleavage of RIPK3 after Asp333 is dispensable for mouse embryogenesis. Cell Death Differ. 2024 Feb;31(2):254-262. doi: 10.1038/s41418-023-01255-5. Epub 2024 Jan 8. PMID: 38191748; PMCID: PMC10850060.
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Liu Z, Garcia Reino EJ, Harschnitz O, Guo H, Chan YH, Khobrekar NV, Hasek ML, Dobbs K, Rinchai D, Materna M, Matuozzo D, Lee D, Bastard P, Chen J, Lee YS, Kim SK, Zhao S, Amin P, Lorenzo L, Seeleuthner Y, Chevalier R, Mazzola L, Gay C, Stephan JL, Milisavljevic B, Boucherit S, Rozenberg F, Perez de Diego R, Dix RD, Marr N, Béziat V, Cobat A, Aubart M, Abel L, Chabrier S, Smith GA, Notarangelo LD, Mocarski ES, Studer L, Casanova JL, Zhang SY. Encephalitis and poor neuronal death-mediated control of herpes simplex virus in human inherited RIPK3 deficiency. Sci Immunol. 2023 Apr 21;8(82):eade2860. doi: 10.1126/sciimmunol.ade2860. Epub 2023 Apr 21. PMID: 37083451; PMCID: PMC10337828.
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Guo H, Koehler HS, Mocarski ES, Dix RD. RIPK3 and caspase 8 collaborate to limit herpes simplex encephalitis. PLoS Pathog. 2022 Sep 19;18(9):e1010857. doi: 10.1371/journal.ppat.1010857. PMID: 36121858; PMCID: PMC9521923.
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Rebecca K Lane*, Hongyan Guo*†, Amanda D Fisher, Jonathan Diep, Zhao Lai, Yidong Chen, Jason W Upton, Jan Carette, Edward S Mocarski, William J Kaiser. Necroptosis-based CRISPR knockout screen reveals Neuropilin-1 as a critical host factor for early stages of murine cytomegalovirus infection. Proc Natl Acad Sci USA 117 (33), 20109-20116. 2020 Aug 18.
- Hongyan Guo, Ryan P Gilley, Amanda Fisher, Rebecca Lane, Vanessa J Landsteiner, Katherine B Ragan, Cole M Dovey, Jan E Carette, Jason W Upton, Edward S Mocarski, William J Kaiser. Species-independent contribution of ZBP1/DAI/DLM-1-triggered necroptosis in host defense against HSV1. Cell death & disease 9 (8), 1-11. 2018 July 26.
- Hongyan Guo, William J Kaiser. ESCRTing necroptosis. Cell 169 (2), 186-187. 2017 April 6.
- Hongyan Guo, Shinya Omoto, Philip A Harris, Joshua N Finger, John Bertin, Peter J Gough, William J Kaiser, Edward S Mocarski. Herpes simplex virus suppresses necroptosis in human cells. Cell host & microbe 17 (2), 243-251. 2015 Feb 11
- Pratyusha Mandal, Scott B Berger, Sirika Pillay, Kenta Moriwaki, Chunzi Huang, Hongyan Guo, John D Lich, Joshua Finger, Viera Kasparcova, Bart Votta, Michael Ouellette, Bryan W King, David Wisnoski, Ami S Lakdawala, Michael P DeMartino, Linda N Casillas, Pamela A Haile, Clark A Sehon, Robert W Marquis, Jason Upton, Lisa P Daley-Bauer, Linda Roback, Nancy Ramia, Cole M Dovey, Jan E Carette, Francis Ka-Ming Chan, John Bertin, Peter J Gough, Edward S Mocarski, William J Kaiser. RIP3 induces apoptosis independent of pronecrotic kinase activity. Molecular cell 56 (4), 481-495. 2014 Nov
Team
Shuqi Wang, MD, PhD
Postdoctoral Fellow in Microbiology and Immunology
EDUCATION
Fudan University, MD & PhD
RESEARCH
My research focuses on understanding the complex interactions between myeloid cells and host-pathogen defense mechanisms, particularly in the context of viral infections. I am interested in exploring the special role of cell death in immune responses and its impact on host defense. One of the key areas of my work is investigating how these cellular processes shape the outcome of viral infections in the central nervous system. By elucidating the molecular mechanisms underlying cell death of myeloid cells and its subsequent effect on the immune response, I aim to contribute to the development of therapeutic strategies to better manage viral encephalitis and enhance host defense against infectious diseases.
Oluwamuyiwa (Timothy) Amusan, B.Sc.
Graduate Assistant in Microbiology & Immunology
EDUCATION
BSc, Microbiology, Obafemi Awolowo University, Ile-Ife, Nigeria
RESEARCH
Z-NA binding protein 1 (ZBP1) is an innate immune sensor that mediates necroptosis (a form of programmed cell death), apoptosis, and inflammation. Although the ZBP1 signaling activation restricts a range of viruses, over-activation of this pathway can lead to fatal immunopathologies such as Aicardi-Goutières syndrome (AGS). Hence, understanding the mechanisms of ZBP1 signaling and activation is crucial. In line with this, we previously showed in the lab that receptor-interacting protein (RIP) kinase (RIPK)1, an important cell-death signaling protein, is essential for virus-triggered ZBP1-mediated necroptosis in human cells. This further highlights RIPK1 (whose inhibitors are already in clinical trials) as a promising therapeutic target for critical ZBP1-mediated immunopathologies. My current project focuses on understanding the mechanism of ZBP1 activation and its functional consequences using Herpes Simplex Virus (HSV) as a trigger. We hope to uncover novel insights that may be crucial for developing therapeutics for ZBP1-mediated diseases.
AWARDS & FELLOWSHIPS
- Second Place Poster Presentation Award (Junior Category), Graduate Research Day, LSUHS, 2023.
- Mingyu Ding Travel Award (2024), Department of Microbiology and Immunology, LSUHS
- Ike Muslow Predoctoral Fellowship, 2024-2025
Positions
We are constantly looking for talented graduate students and post-doctoral fellows to join our program. We are offering a highly collaborative work environment, competitive compensation and highly innovative research projects.
Students interested in working in our Department should visit our Graduate Program website.
Contact
Contact Us
LSU Health Shreveport
Department of Microbiology & Immunology
1501 Kings Hwy
Shreveport, LA 71103
Email: Hongyan.Guo@lsuhs.edu
Office: 318-675-5701
Guo Lab
