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Topic Overview:

Immune cells, like T cells, are integrated throughout the body where signals from microbial, metabolic, and environmental antigen exposure create tissue-specific niches that can modulate the immune response. T cells play critical roles to fight infection; however, dysregulation of T cells against innocuous stimuli can lead to allergic or autoimmune responses that are often tissue-specific in nature. Poholek’s research seeks to understand how T cells integrate tissue-specific signals to control T cell function and limit autoimmunity.

Poholek’s recent study uncovered a tissue-specific function for the transcriptional repressor Blimp-1 in T cells to promote allergic asthma in the context of commonly inhaled allergens, like house dust mites. Blimp-1 can also constrain effector T cells in the colon to limit autoimmune colitis, suggesting tissue-specific signals regulate Blimp-1-dependent pathways to control T cell function. Poholek’s work is exploring the cell-type and context-dependent expression and function of Blimp-1 as a means to understand how individual tissue-specific niches regulate T cells at the transcriptional level.

Epigenetic regulation controls transcriptional pathways and is also critical for T cell function. Using Nextgen sequencing technologies, Poholek is exploring the epigenetic landscapes in T cells. Together with Greg Delgoffe, PhD, associate professor of immunology, School of Medicine, Poholek has uncovered tumor-specific signals that contribute to altered epigenetic landscapes in T cells, which drive dysfunctional T cells that contribute to pro-tumor immunity and limit responses to cancer immunotherapy. Studies aimed to further understand how tumor-specific factors control epigenetic regulation of T cells leading to dysfunction is an area of current study in Poholek’s lab.