Ryan Zander
Chronic viral infections, such as HIV-1 and hepatitis B and C virus, continue to affect hundreds of millions of people worldwide and result in over 2 million deaths annually. Viral persistence is usually associated with impaired T cell responses and a paucity in the development of neutralizing antibody titers. Although CD4+ T cells play a critical role in sustaining both CD8+ T cell responses and humoral immunity, most research to date has focused on understanding the mechanisms that drive CD8+ T cell “exhaustion,” a differentiation process characterized by the upregulation of multiple co-inhibitory receptors and loss of effector function. Notably, T cell exhaustion also commonly occurs during multiple forms of cancer, thereby highlighting the generalizability of this differentiation process. Importantly, recent evidence indicates that CD4+ T cells play an essential role in limiting T cell exhaustion and sustaining the function of CD8+ T cells during both chronic infection and cancer. However, our understanding of how persistent exposure to antigen and inflammation shapes CD4+ T cell differentiation remains incompletely understood.
My research is focused on determining the environmental cues, transcriptional networks, and epigenetic circuits that regulate the differentiation and effector function of virus and tumor-specific CD4+ T cells. Moreover, I seek to dissect the molecular mechanisms by which CD4+ T cells interact with other immune cell subsets, (such as DCs, B cells, and CD8+ T cells) to facilitate protective immunity, and to identify how CD4+ T cell “help” impacts the overall immune landscape during persistent infection. Past and current projects have employed the use of advanced protocols in cellular and molecular immunology as well as in vivo models of lymphocytic choriomeningitis (LCMV) infection and tumorigenesis to interrogate T cell responses that develop in the face of persistent antigen exposure and inflammation. My long-term goals are to use the information I learn in experimental models to directly inform human studies, which will significantly aid in the development of novel strategies to effectively combat chronic infections and cancer in humans.
- Adaptive immunity
- Cancer immunology
- Cell differentiation
- Immune memory
- T cell Biology
- Viruses