Man Hing Li
Assistant Professor, MIMG, University of California Los Angeles
The host innate immune response is the first line of defense against viral infections. Cytosolic sensors in the host cell recognize the incoming virus and stimulate the production of types I and III interferons (IFNs) with direct antiviral activities. The same or neighboring cell binds secreted IFNs and triggers the JAK/STAT signaling pathway resulting in the expression of a wide array of IFN-stimulated genes (ISGs). Many of these ISGs target different steps of the viral life cycle, but only some of them have been characterized. A main focus of the Li Lab is to elucidate the mechanisms of antiviral IFNs and ISGs using molecular biology, biochemistry, genome-wide approaches, and stem cell culture systems. We are studying the host and viral determinants that modulate viral infections in the presence of antiviral ISGs in different cell contexts using arthropod-borne alphaviruses as our model system. Several projects in the lab focus on the mechanism of zinc finger antiviral protein (ZAP), a broad-spectrum antiviral ISG that inhibits a broad range of viruses, and how it synergizes with its co-factor, the host E3 ubiquitin ligase TRIM25. Understanding the antiviral mechanisms of ISGs not only will shed light on how the host distinguishes between self and non-self, but it will also uncover viral antagonism strategies of the host innate immune response that drive increased viral virulence and pathogenesis.
Education and Training
|The Rockefeller University||08/2017||Virology|
|University of Washington, Seattle||Ph.D.||04/2011||Microbiology|
|University of California, Irvine||B.S.||03/2006||Biological Sciences|
- Yang E, Huang S, Jami-Alahmadi Y, McInerney GM, Wohlschlegel JA, Li MMH. Elucidation of TRIM25 ubiquitination targets involved in diverse cellular and antiviral processes.. PLoS pathogens, 2022.
- Li M, Dai L, Hu Y. Machine Learning for Harnessing Thermal Energy: From Materials Discovery to System Optimization.. ACS energy letters, 2022.
- Yang E, Nguyen LP, Wisherop CA, Kan RL, Li MMH. The Role of ZAP and TRIM25 RNA Binding in Restricting Viral Translation.. Frontiers in cellular and infection microbiology, 2022.
- Cheng Y, Medina A, Yao Z, Basu M, Natekar JP, Lang J, Sanchez E, Nkembo MB, Xu C, Qian X, Nguyen PTT, Wen Z, Song H, Ming GL, Kumar M, Brinton MA, Li MMH, Tang H. Intrinsic antiviral immunity of barrier cells revealed by an iPSC-derived blood-brain barrier cellular model.. Cell reports, 2022.
- Luu AP, Yao Z, Ramachandran S, Azzopardi SA, Miles LA, Schneider WM, Hoffmann HH, Bozzacco L, Garcia G, Gong D, Damoiseaux R, Tang H, Morizono K, Rudin CM, Sun R, Arumugaswami V, Poirier JT, MacDonald MR, Rice CM, Li MMH. A CRISPR Activation Screen Identifies an Atypical Rho GTPase That Enhances Zika Viral Entry.. Viruses, 2021.
- Yang E, Li MMH. All About the RNA: Interferon-Stimulated Genes That Interfere With Viral RNA Processes.. Frontiers in immunology, 2020.
- Garcia G, Paul S, Beshara S, Ramanujan VK, Ramaiah A, Nielsen-Saines K, Li MMH, French SW, Morizono K, Kumar A, Arumugaswami V. Hippo Signaling Pathway Has a Critical Role in Zika Virus Replication and in the Pathogenesis of Neuroinflammation.. The American journal of pathology, 2020.
- Li MMH, Aguilar EG, Michailidis E, Pabon J, Park P, Wu X, de Jong YP, Schneider WM, Molina H, Rice CM, MacDonald MR. Characterization of Novel Splice Variants of Zinc Finger Antiviral Protein (ZAP).. Journal of virology, 2019.
- Law LMJ, Razooky BS, Li MMH, You S, Jurado A, Rice CM, MacDonald MR. ZAP's stress granule localization is correlated with its antiviral activity and induced by virus replication.. PLoS pathogens, 2019.
- Wu X, Dao Thi VL, Huang Y, Billerbeck E, Saha D, Hoffmann HH, Wang Y, Silva LAV, Sarbanes S, Sun T, Andrus L, Yu Y, Quirk C, Li M, MacDonald MR, Schneider WM, An X, Rosenberg BR, Rice CM. Intrinsic Immunity Shapes Viral Resistance of Stem Cells.. Cell, 2017.
- Li MM, Lau Z, Cheung P, Aguilar EG, Schneider WM, Bozzacco L, Molina H, Buehler E, Takaoka A, Rice CM, Felsenfeld DP, MacDonald MR. TRIM25 Enhances the Antiviral Action of Zinc-Finger Antiviral Protein (ZAP).. PLoS pathogens, 2017.
- Li MM, Bozzacco L, Hoffmann HH, Breton G, Loschko J, Xiao JW, Monette S, Rice CM, MacDonald MR. Interferon regulatory factor 2 protects mice from lethal viral neuroinvasion.. The Journal of experimental medicine, 2016.
- Wang X, Li MMH, Zhao J, Li S, MacDonald MR, Rice CM, Gao X, Gao G. Sindbis Virus Can Exploit a Host Antiviral Protein To Evade Immune Surveillance.. Journal of virology, 2016.
- Li MM, MacDonald MR. Polyamines: Small Molecules with a Big Role in Promoting Virus Infection.. Cell host & microbe, 2016.
- Bozzacco L, Yi Z, Andreo U, Conklin CR, Li MM, Rice CM, MacDonald MR. Chaperone-Assisted Protein Folding Is Critical for Yellow Fever Virus NS3/4A Cleavage and Replication.. Journal of virology, 2016.
- Li MM, MacDonald MR, Rice CM. To translate, or not to translate: viral and host mRNA regulation by interferon-stimulated genes.. Trends in cell biology, 2015.
- Charron G, Li MM, MacDonald MR, Hang HC. Prenylome profiling reveals S-farnesylation is crucial for membrane targeting and antiviral activity of ZAP long-isoform.. Proceedings of the National Academy of Sciences of the United States of America, 2013.
- Karki S, Li MM, Schoggins JW, Tian S, Rice CM, MacDonald MR. Multiple interferon stimulated genes synergize with the zinc finger antiviral protein to mediate anti-alphavirus activity.. PloS one, 2012.
- Li MM, Emerman M. Polymorphism in human APOBEC3H affects a phenotype dominant for subcellular localization and antiviral activity.. Journal of virology, 2011.
- Li MM, Wu LI, Emerman M. The range of human APOBEC3H sensitivity to lentiviral Vif proteins.. Journal of virology, 2010.
- OhAinle M, Kerns JA, Li MM, Malik HS, Emerman M. Antiretroelement activity of APOBEC3H was lost twice in recent human evolution.. Cell host & microbe, 2008.