CAREER: Systems Immunology Approach to Memory T Cell Immune Engineering

PI: Jiang , Ning Proposal No: 1653866

The principal investigator will examine a fundamental question in immunology, namely how memory T cells, a cell type present in blood responsible for immune protection, are selected. Successful application of new knowledge gained is expected to provide new tools for immunotherapy. It is also planned to develop campus-wide course on immune engineering aimed at freshman undergraduates for non-STEM majors.

The goal of engineering of vaccine and immune therapy for pathogens and cancers is to achieve long-term immune memory, which is maintained by memory T and B cells. Among various B and T cell subtypes, the long lasting CD8+ T cell memory is an attractive target because of its high specificity, exquisite sensitivity, and durable killing effect. High affinity T cell receptor-based T cell engineering has shown great therapeutic potential in cancer and persistent viral infection.

However, a critical problem is how to educate these T cells to properly form memory. Since microRNAs have been implicated in many biological processes including memory T cell generation and their expression levels are easy to manipulate, we aim to combine several recently developed technologies in T cell profiling to systematically study the role of microRNA regulatory network in engineering T cell memory in this proposal.

By interrogating T cell receptor binding strength dictated microRNA regulatory networks, our goal is to identify top microRNA regulatory nodes and manipulate and test their importance to engineering T cell memory. At the same time, it is proposed to leverage research effort to build an educational program in immune engineering. Through a new campus-wide course aimed at freshman undergraduates in non-STEM majors and associated activities including student-generated concepts for "engineer T cell immunity" and presentations to local middle and high school students, our educational activities will broaden participation in science on our campus and in our community, while simultaneously enhancing our proposed research efforts.

Thus, the proposed project creates a synergistic integration of research activities, educational activities, and outreach to the community.