Dr. Kazuki Nagashima

The human intestine is exposed to a vast array of molecules from the microbiome, diet, and pathogens. The Nagashima lab focuses on three branches of research topics, all of which attempt to understand the gut immune system at the level of molecular mechanisms. 

(1) Building a model system of the gut microbiome. Many previous studies characterized the function of gut bacteria under the artificial condition of mono-colonization using germ-free mice. However, it is unknown how each bacterial strain affects the immune system in the context of a bacterial community.  To address this question, we are developing a synthetic model of the gut microbiome with >100 strains.

(2) Exploring T cell response at the repertoire level. T cells orchestrate the immune responses by recognizing a molecular cue, an antigen, from bacteria and diet using the T cell receptor (TCR). However, our current understanding of T-cell responses in the gut is based on a small subset of bacteria and dietary antigens, like SFB and OVA. We map individual TCRs to numerous antigens in the physiological condition of a bacterial community and complex diet. 

(3) Identify dietary molecules that induce T cell response. The diet has been established as one of the most efficient ways to prevent human disease. Yet, the underlying molecular pinnings are not well understood. Our study discovers the role of dietary molecules in T cell induction and paves the pathway for new therapeutic strategies in which diet-specific immune responses are logically manipulated.