Transcriptional regulation of cell development and function in the immune system
Cellular quiescence is a state characterized by small cell size, lack of spontaneous proliferation, and reduced metabolic rate. Even in the absence of overt antigen challenge, circumstances such as lymphopenia, or the ablation of inhibitory receptors or regulatory T (Treg) cells, can drive quiescent naive T cells to undergo proliferation, gain effector functions and often lead to autoimmune diseases. These observations indicate that lymphocyte quiescence does not occur by default, but is actively maintained by both extrinsic and intrinsic mechanisms, which are poorly understood at the molecular level. Recently we have identified forkhead box (FOX) transcription factor Foxp1 as an essential regulator in maintaining mature T cell quiescence, providing direct evidence that lymphocyte quiescence is actively controlled at the transcriptional level. One goal of the laboratory is to identify novel regulatory genes/networks of T cell quiescence and determine their roles in T cell homeostasis, tolerance, and immune responses.
Hematopoiesis engages hierarchical regulatory networks of key transcription factors that exert positive and negative impacts on gene transcription by changing chromatin status and structure and determine cell “fate” at critical developmental and differentiation stages. This line of the research in our laboratory is to understand the hierarchical transcriptional regulation in hematopoiesis/lymphopoiesis.
Our laboratory utilizes a broad variety of techniques including cellular immunology, molecular biology, biochemistry, gene-targeting (knockout and knockin), functional genomics, and in vivo animal models to address the questions that we are interested in.
Research projects in the laboratory include:
1) Foxp1 transcriptional network in maintaining mature T cell quiescence.
2) Crosstalk between the mechanism of T cell quiescence and the mechanism of agonist-induced T cell activation, and the impact of such interactions on T effector differentiation and memory formation in infectious disease models.
3) Tumor microenvironmental regulation of T cell unresponsiveness/quiescence.
4) Transcriptional regulation in early B cell development and mature B cell functions.
5) Transcriptional regulatory networks in hematopoiesis/lymphopoiesis.