Myung Hee (Michelle) Kim, B.S.
Graduate Research Assistant
Office: BME 5.412
mhk58@mail.utexas.edu

Research Focus: Notch Signaling through Polymer Scaffolds for T Cell Differentiation

Use of cell immunotherapy is known to have a tremendous range of possibilities in treating diseases. However, in order for this dream to become a clinical reality, an efficient, high-throughput method to produce the cells is needed. Hematopoietic stem cells (HSCs) and T cells can be isolated from patients, but inefficiently and with high morbidity. Efficient expansion and differentiation of HSCs in a synthetic environment is needed. We propose a three-dimensional environment for T cell lineage commitment. It is well known that notch ligands in the thymic stromal environment direct T cell commitment of hematopoietic stem cells, and that immobilization of such ligands are required, together with soluble factors from stromal cells. Our goal is to fabricate a polymer architecture that will present notch ligands to HSCs and direct early T cell lineage commitment in vitro. The polymer scaffold will be composed of ECM proteins to mimic the biological thymic environment and provide immobilized notch ligands to T cells. A scaffold will also allow the T cell to be physically segregated from the stromal cells, allowing them to receive the soluble factors secreted by the stromal cells and yet able to be separated from those cells easily. Such a three-dimensional structure will allow easy retrieval of T cells when needed, for analysis and for usage, if the polymer is chemically degradable. Eventually we hope to incorporate the tetramer-based system for antigen presentation to produce antigen-specific T cells. We hope that these studies will not only explore a novel, efficient way to differentiate T cells in vitro, but also provide a better understanding of the thymic environment and the biology of notch signaling in T cell differentiation.