|Assistant Professor, Microbiology, Immunology & Molecular Genetics|
|Member, CTSI, Genetics & Genomics GPB Home Area, Immunity, Microbes & Molecular Pathogenesis GPB Home Area|
Mosquito-borne viruses are emerging pathogens that cause devastating outbreaks worldwide as globalization and climate change facilitate their spread beyond their endemic regions. The Li laboratory studies the host type I interferon (IFN) response to medically relevant mosquito-borne viruses such as alphaviruses and flaviviruses. Cellular sensing of viral pathogens triggers IFN production and signaling leading to expression of a wide array of IFN-stimulated genes (ISGs) with antiviral activities. In particular, zinc finger antiviral protein (ZAP) targets diverse viruses by recognition of CG dinucleotide, recruitment of cellular RNA decay machineries, and suppression of viral translation. However, what determines the broad yet specific activity of ZAP is poorly understood. We discovered that ZAP co-opts the host ubiquitination pathway to block viral translation, and some alphaviruses have evolved strategies to evade ZAP antiviral action. Understanding how cellular and viral processes modulate ISG antiviral function will shed light on the molecular mechanisms driving viral virulence and pathogenesis. In addition, recent studies by other groups have pointed to an unexpected role of IFNs; both type I and type III IFNs can decrease blood-brain barrier permeability in a mouse viral infection model. We are interested in the pro-barrier functions of IFNs as our previous work suggested that IRF2, a negative regulator of IFN, protects the central nervous system from alphaviral invasion and encephalitis. A full characterization of ISG activities will elucidate the basic biology of host pathogen recognition and uncover cellular processes required for the success or suppression of viral replication, which will inform the development of broad-spectrum antiviral therapeutic.
Dr. Li is an Assistant Professor of Microbiology, Immunology and Molecular Genetics at UCLA. She received her Bachelors of Science Degree (B.S.) from University of California, Irvine in 2006, and her Doctor of Philosophy Degree (Ph.D.) in Microbiology from University of Washington, Seattle in 2011. Dr. Li’s thesis work elucidated the functional consequences of polymorphisms in the human APOBEC3H gene, which encodes for a cytosine deaminase that is antiviral against human immunodeficiency virus type 1 (HIV-1). Dr. Li subsequently completed her postdoctoral work at Rockefeller University where she studied the antiviral mechanisms and regulation of the host interferon response targeting alphaviruses. Dr. Li established her own laboratory at UCLA in 2017, and her research focuses on elucidating the role of ISGs in innate immunity and blood-brain barrier integrity with broad implications for the treatment of viral infections, autoimmunity and neurological diseases. She serves on the UCLA Basic/Translational COVID-19 Research Committee.