Research interest: Innate Immunity, Viral Immunology, Mosquito-Borne Viral Disease, Respiratory Viral Disease, COVID-19, SARS-CoV-2. 

Research support: NIH R01AI132526, R21AI155820

Immunity to Viral Infection

My laboratory is  interested in host-virus interactions, with a focus on RNA viruses in vivo and in vitro. Specifically, we attempt to understand pathogenic mechanisms of viral infection at the cellular and animal levels, and study the molecular function of host genes that influence viral pathogenesis and the disease outcomes. On the host end, we are keen on the innate immune system, detection of viruses and initiation of innate antiviral immune responses.  On the viral end, we hope to understand the mechanisms of immune evasion and modulation of cellular functions by viral proteins. 

 1.    The physiological functions of UBXNs in antiviral immunity. The human genome encodes 13 ubiquitin regulatory X (UBX) domain-containing proteins, designated UBXNs. The UBX domain shares weak homology with ubiquitin at the protein level and adopts the same three dimensional fold as ubiquitin. A number of UBXNs have been shown to bind to multiple E3 ubiquitin ligases and the ATPase associated with various cellular activities (AAA ATPase), p97, which is highly conserved across species and involved in diverse cellular processes, including ER-associated degradation (ERAD), vesicle fusion/membrane trafficking, and cell cycle. We and other research groups have recently shown that several UBXNs regulate the pattern recognition receptor (PRR) signaling including the viral RNA sensor RIG-I – MAVS axis (Retinoic acid Inducible Gene-Mitochondrial Antiviral Viral Signaling), the dsDNA sensor cGAS-STING axis (cyclic di-GMP-AMP Synthase-- Stimulator of Interferon Genes), and NF-kB signaling pathways. We are now elucidating the physiological functions of several UBXNs (Ubxn1, Ubxn3b and Ubxn9) during viral infection (arthritogenic alpahviruses: Chikungunya and O’nyong nyong, respiratory viruses: influenza and SARS-CoV-2) in tamoxifen-inducible gene knockout mice. 

2.    The roles of E3 ubiquitin ligases in viral pathogenesis and immune regulation. Ubiquitination is one of the best characterized and most important post-translational modifications that controls protein function and/or fate and impacts almost all cellular pathways, including viral pathogenesis. Ubiquitination is executed by three enzymes: ubiquitin-activating E1 (two genes in human genome), ubiquitin-conjugating E2 (~40 genes), and ubiquitin E3 ligases (~500) that determine substrate specificity. The ubiquitin-conjugating system impacts viral pathogenesis either directly by interfering with viral life cycle (including entry, replication, translation, assembly, egress) or indirectly by regulating antiviral immune responses. The host ubiquitination machinery can also be co-opted by viruses to complete their life cycle. We have generated a library of 374 individual E3 ligase knockout cell lines using CRSIPR-Cas9 and now systemically examining their functions in pattern recognition receptor (PRR) signaling and viral pathogenesis (influenza, SARS-CoV-2).   

Accepting Lab Rotation Students: Fall 2022 and Spring 2023

Journal Articles

Reviews