The main interest of the Barski Laboratory is to understand how the T-cell epigenome regulates the function of T cells. Activation of T cells is an essential step in the immunological response to infection. Activation of naive T cells results in proliferation and slow differentiation into cytokine-producing effector cells, whereas antigen engagement with memory cells leads to cytokine production immediately. Even though the cell surface signaling events are similar in both cases, the outcome is different, suggesting that distinct regulatory mechanisms may exist downstream of the activation signals.
Recent advances in the understanding of global epigenetic patterns in T cells have resulted in the appreciation of the role of epigenetic mechanisms in processes such as activation and differentiation. Recent data suggest that naive T-cell activation, differentiation and lineage commitment result in epigenetic changes. On the other hand, memory T cells are epigenetically poised and do not require epigenetic changes for short-term activation. We hypothesize that this epigenetic poising underlies the rapid recall ability of memory T cells.
Currently, we are focused on understanding the epigenetic mechanisms that underlie the functions of different subsets of human T cells. We are also interested in the epigenetic basis of peripheral T-cell tolerance. Additionally, we are collaborating with John Harley’s group to understand the epigenetic basis of lupus and with Satoshi Namekawa's group to understand epigenetic regulation in germ cells.