Yifei Liao

Start Date: March 1, 2027

Assistant Professor of Virology, Immunology & Microbiology

Research Interest

My long-term interest is to integrate CRISPR genome editing, multi-omics, and three-dimensional culture (air-liquid interface and organoid models) approaches to study herpesvirus-host interactions in lymphocytes and epithelial cells. Epstein-Barr virus (EBV) is the most common human gamma-herpesvirus that infects over 90% of adults. EBV infection causes infectious mononucleosis and is associated with various lymphomas, including Burkitt lymphoma and Hodgkin lymphoma. EBV also associates with several epithelial malignancies, including nasopharyngeal carcinoma and gastric cancer, and is a major viral trigger of multiple sclerosis. My laboratory will particularly focus on metabolic and epigenetic controls of EBV lifecycle in carcinomas and lymphoproliferative diseases. Building on prior CRISPR-Cas9 screens, I revealed major and unexpected NAD+ metabolism roles in support of EBV lytic gene expression. My current research focuses on role of host NAD+ metabolism and epigenetics in EBV lytic cycle. As recently funded NIDCR K99/R00 Pathway to Independence Award, I will utilize systematic genomic, metabolomic and proteomic approaches to investigate how EBV lytic cycle is regulated, which will lay a foundation for host metabolism targeted antiviral agents that broadly block EBV lytic gene expression. The ultimate goal is to identify novel therapeutics targets for EBV-associated diseases.

My graduate studies in Dr. Blanca Lupiani and Dr. Sanjay Reddy’s laboratory at Texas A&M University focused on Marek’s disease virus (MDV), a major cause of rapid onset of T-cell lymphoma in chickens and is a major challenge for the poultry industry. I identified key MDV encoded US3 protein phosphorylation targets and interaction partners, characterized US3 roles in gene expression regulation, and elucidated US3 roles in MDV replication and oncogenesis. These studies provided the first evidence that US3 is important in both the replication and pathogenicity of MDV in its natural host. In my laboratory, I’m also interested in extending my MDV research to further understand its pathogenesis and tumorigenesis and develop next-generation vaccines. MDV could also be utilized as a valuable natural infection small animal model for human herpesvirus research.

My postdoctoral studies in Dr. Benjamin Gewurz’s laboratory at Brigham and Women’s Hospital were initially supported by a Lymphoma Research Foundation post-doctoral fellowship, where I characterized how EBV epigenetically switches between latency programs as it navigates the B-cell compartment. I am then particularly interested in the longstanding question of how host factors restrict and support EBV lytic cycle in EBV-associated cancers. In depth understanding of the mechanisms behind EBV reactivation and replication could help to identify potential druggable targets of EBV+ cancer for lytic induction therapy. I performed parallel human genome-wide CRISPR-Cas9 screens for Burkitt lymphoma factors critical for EBV latency and for lytic replication and demonstrated that the lysine specific histone demethylase LSD1 and its co-factors, zinc finger protein ZNF217 and the co-repressor CoREST role in EBV lytic reactivation by regulating H3K4 methylation on EBV lytic promoters and enhancers. I also found that LSD1 inhibition sensitized Burkitt cells to ganciclovir cytotoxicity, suggesting a novel therapeutic approach for EBV associated cancers. Further, in collaboration with colleagues, we leveraged multi-omic approaches to reveal the existence of pro-latency and pro-lytic viral long noncoding RNAs (lncRNAs) that counter-regulate the EBV lytic switch. We further characterized that the pro-lytic lncRNA occupies viral origin of lytic replication enhancers and promotes their looping to the immediate early lytic promoter to trigger EBV reactivation. We also identified the EBV-encoded BALF0/1 that targets the immunoglobulin B-cell receptor complex for degradation upon viral reactivation.