Research
Deep-profiling tissue-resident memory T cells during viral infection and virus-associated cancer
Current knowledge of human T cell biology is often limited to the study of total T cell population without the understanding of antigen-specific immunity due to the lack of apparent T cell epitopes. In addition, most of the studies only investigate peripheral T cells without encompassing site-specific responses in human tissues, where the diseases usually occur. These prevent the accurate interpretation of disease-specific immune responses and restrain the therapeutic implications of findings. Our goal is to dissect the complexity of virus-specific CD8+ T cell responses detected in healthy versus diseased blood and tissue samples. We are particularly interested in chronic viral (e.g., hepatitis B virus, HBV) infection, HBV-associated liver diseases, and SARS-CoV-2 infection. Combining the usages of highly multiplexed combinatorial peptide-MHC tetramer staining, mass cytometry, and other single-cell multi-omics, we aim to comprehensively investigate the T cell antigen-specificities, virus-reactive T cell receptors (TCR), and cellular phenotypes across human tissues, with a focus on the characteristics of tissue-resident memory T (TRM) cells and exhausted T (TEX) cells. We believe our work can facilitate the fundamental understanding of human T cell biology, improve immunotherapeutics against cancer, and advance the next generation of vaccine design.
JRNLclub talk
Probing virus-specific CD4+ T cells and the long-term immune protection induced by viral infection or vaccination
As the central component of human adaptive immunity, CD4+ “helper” T cells are essential for the generation and maintenance of robust cellular (CD8+ T cell) and humoral (B cell and antibody) immune responses. Our goal is to use peptide-MHCII tetramer and antigen-probe to identify the relevant virus-specific CD4+ T cell subset (e.g., follicular helper T cells, TFH) and the interacting virus-specific B cells that confer long-term immune protection during the event of viral antigen seroconversion or vaccination.
Early life immunity upon emerging viral infection or vaccination
Newborn immune system is greatly shaped by early exposure of pathogens or immunization through early life. We want to uncover the underlying immunological basis that regulate virus-specific immune response in utero and long-term immune protection of newborn. Our objective is to decipher the maternal-fetal immune interaction, describe the important adaptive immune networks, and establish the key features of memory T cells upon viral infection or vaccination (e.g., SARS-CoV-2 and HBV) in barrier or mucosal tissues during early phase of human life.
Using cutting-edge methods to explore and visualize the high-dimensional complexity of immune cells
The lab is experienced in combining the utility of mass cytometry (CyTOF), high-parameter spectral flow cytometry, single-cell analytical tools, and high-dimensional analysis, to delve into the biological insights of human immune responses.