Transcription and epigenetic regulation of T cell function, self-renewal of hematopoietic and leukemic stem cells
T lymphocytes have versatile functions in host immune responses. We are interested in transcriptional and epigenetic regulation of T cell development and mature T cell responses to infections. Our current focus is on Tcf1 and Lef1 transcription factors in the Tcf/Lef family, their interacting partners including the - and -catenin coactivators and TLE corepressors. We are using gene targeting, molecular biology, and bioinformatics approaches to dissect how they cooperatively regulate 1) T cell lineage commitment and identity maintenance in the thymus and 2) acquisition of effector T cell function upon activation and transition to memory T cells with enhanced protective capacity. We aim to gain insights into immune regulation and modulate T cell function for therapeutic applications. Another major interest in the lab is to identify common and distinct regulatory modules between hematopoietic and leukemia stem cells (HSCs and LSCs). We are using animal models of chronic and acute myeloid leukemia to characterize the molecular basis of LSC self-renewal. Using transcriptional program as a therapeutic target, we aim to identify small molecules that specifically impair LSCs but with minimal impact on normal HSCs.