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Koichi Araki


Research Interests

To develop a successful vaccine against pathogens such as HIV, HCV, malaria etc., it will be essential for the vaccine to induce not only neutralizing antibodies but also highly protective memory T cells that persist for a long time and quickly react once they encounter pathogens. These functional memory T cells are known to be generated after acute infections in which pathogens are cleared within 1~2 weeks. Thus, it is important to understand how functional memory T cells are induced from naïve T cells during acute infections. Recently, our study has uncovered that mTOR plays a critical role in memory CD8 T cell differentiation. mTOR is an evolutionally conserved serine/threonine kinase and regulates cell growth and proliferation. We found that inhibiting mTOR during CD8 T cell responses not only enhanced quantity of memory CD8 T cells but also improved quantity of them. Our study has implications that mTOR is a potential intracellular target to enhance vaccine-induced T cell memory. Our current efforts focus on understanding of molecular and cellular mechanisms by which mTOR pathways regulate memory CD8 T cell differentiation. We also study potential application of our findings in a clinical setting.

Selected Publications

1          Araki, K., Turner, A. P., Shaffer, V. O., Gangappa, S., Keller, S. A., Bachmann, M. F., Larsen, C. P. and Ahmed, R., mTOR regulates memory CD8 T-cell differentiation. Nature 2009. 460: 108-112.

2          Araki, K., Youngblood, B. and Ahmed, R., The role of mTOR in memory CD8 T-cell differentiation. Immunol Rev 2010. 235: 234-243.

3          Araki, K., Gangappa, S., Dillehay, D. L., Rouse, B. T., Larsen, C. P. and Ahmed, R., Pathogenic virus-specific T cells cause disease during treatment with the calcineurin inhibitor FK506: implications for transplantation. J Exp Med 2010. 207: 2355-2367.

4          Araki, K., Ellebedy, A. H. and Ahmed, R., TOR in the immune system. Curr Opin Cell Biol 2011. 23: 707-715.

5          Araki, K. and Konieczny, B. T., Utilizing a retroviral RNAi system to investigate in vivo mTOR functions in T cells. Methods Mol Biol 2012. 821: 305-316.

Research Topics