Epigenetic mechanisms governing T cell differentiation

Our laboratory is interested in elucidating fundamental mechanisms that govern heritable states of effector T cell subsets during and after differentiation. We utilize the thymic model of T cell differentiation, which is a unique and tractable system to follow T cell differentiation from common bone-marrow precursors all the way to mature T cells that patrol the periphery. We also utilize various mouse models of infection such as Leishmaniasis and LCMV to dissect mechanisms that shape effector and memory responses in the periphery. In the course of our studies looking at lineage commitment of helper CD4 T cells, we discovered that regulatory cis-elements are intimately involved in shaping the epigenetic landscape of gene transcription. Regulatory cis-elements, which can be in the form of enhancers and silencers, offer temporal control of gene expression and by dictating the timing of gene expression, are able to significantly alter the course of cell differentiation. In addition, they appear to impart key epigenetic features that continue to affect transcription, even when they are no longer active. With the aid of new mouse models and whole genome sequencing technologies, we are exploring the link between regulatory cis-elements and epigenetic remodeling, with the aim of understanding how such mechanisms may be relevant in immunological disease.