Research Summary

The Zhang Lab integrates virology, molecular and cellular biology, genomics, immunology, and pathology to investigate fundamental mechanisms of host-pathogen co-evolution, innate immunity, and cellular reprogramming across three interconnected core areas:

• Virus-Host Interactions & Pathogenesis: Epstein-Barr virus (EBV) is a human herpesvirus associated with human cancers—such as post-transplantation lymphoproliferative disorder (PTLD) and AIDS-associated CNS lymphoma—and autoimmune diseases like systemic lupus erythematosus (SLE) and multiple sclerosis (MS). We focus on host-herpesvirus interactions, innate immune defense, and the functions of Interferon Regulatory Factors (IRFs) in EBV transformation. Dr. Zhang originally discovered IRF-7, identified the first functional interferon-stimulated response element (ISRE) in a mammalian viral promoter, and unearthed a novel signaling pathway in IRF-7 regulation and EBV latency. Using genetic and biochemical approaches, we investigate how cellular factors regulate IRFs in EBV-mediated oncogenesis and how herpesviruses (EBV and KSHV) evade host immunity to drive replication and disease.
• Comparative & Experimental Evolutionary Genomics: We investigate the genomic architecture, evolutionary dynamics, and host-pathogen co-evolution underlying major metazoan transitions. Combining computational phylogenomics and wet-lab experimental approaches, we explore how ancient cellular predator-prey dynamics and genomic instability drove early animal body-plan diversification, as well as the evolutionary pressures and chromosomal dynamics underlying sexual reproduction. Additionally, we apply single-cell genomics and experimental infection assays (e.g., testing viral infection of gametes) to examine viral latency, genomic integration, and long-term host-virus co-evolution.
• Genetic Modification & Personalized hiPSCs: Human induced pluripotent stem cells (hiPSCs) offer remarkable experimental, diagnostic, and therapeutic potential without the ethical concerns of embryonic stem cells. To address ongoing challenges in cell targeting, factor selection, and delivery methods, we develop personalized hiPSC genetic systems for therapeutic modifications and for modeling viral infections and disease pathogenesis.

Specialization: Viral Oncogenesis; Evolutionary Genomics; Stem Cell Biology; Infectious Diseases; Innate Immunity