Costimulation in T lymphocyte memory
Costimulatory signals expressed by professional antigen presenting cells (APCs) are capable of promoting the formation of highly active effector T cells, which are able to develop into memory populations. However, the mechanisms by which constimlation regulate T lymphocyte memory remain uncertain. Several molecular targets of costimulation (e.g., aurora B, survivin, bcl-xL, PKB) have been identified to sustain T cell proliferation or survival, and their cooperation in promoting T cell persistence as well as tumor regression is being investigated. Findings related to this project will provide new insights into why costimulatory signals might need to be sustained over time and suggest a potential novel approach to augment cellular immunotherapy for cancer.

Immune cell differentiation from induced pluripotent stem cells
Most effort is being expended to generate and characterize highly reactive immune cells from induced pluripotent stem (iPS) cells. Because of the plasticity and potentially unlimited capacity for self-renewal, iPS cell-derived immune cells have great potential in the treatment of disease (e.g., cancer, autoimmune disease, infectious disease, aging-related disease). Antigen-specific highly reactive T cells can be generated by genetic modification of iPS cells with specific T cell receptor and costimulation and stimulation with in vitro Notch signaling, and their therapeutic potential in the treatments of cancer and autoimmune disease are being determined. Findings related to this project will contribute important information to the areas of vaccine design, autoimmune therapy, and immune-based anti-cancer strategies.