Current Research
Immune sensing and regulation of distal organs
T cells play a pivotal role in intestinal homeostasis, by sensing and responding to a large variety of intestinal stimuli such as the microbiota and dietary components. The responses not only defend the intestinal barrier but also orchestrate functions of other organs to cope with environmental changes. However, the underlying mechanisms remain largely unknown.
Intestinal T cells could respond to local stimuli by differentiating into specific subtypes and producing characteristic cytokines. T cells and cytokines can then travel to distal organs such as the brain and liver through circulation and exert regulatory functions. In addition, immune signals can also be perceived and relayed by enteric neurons, thereby influencing distal organs via the immune-neural axis. By profiling the expression of cytokine receptors, we are exploring the remote regulatory mechanisms by which intestinal T cells modulate functions of distal organs, including the brain, liver and adipose tissues.
Novel regulators of T cell activities in the gut and in tumors
T cells are regulated by the local microenvironment, which provides immunogenic and modulatory signals for T cell activation and function. To identify novel regulators of T cells, we couple CRISPR/Cas9-based gene silencing and activation with sgRNA libraries targeting genes involved in metabolism and epigenetic regulation. By analyzing modified T cells enriched and depleted in the intestine, we expect to discover novel regulatory mechanisms in T cells. This strategy is currently tested in a simplified tumor model.
