During animal wound healing and tissue regeneration, local wound signals need to propagate a long distance to induce tissue-wide global response to enable regeneration. However, the underlying signal transduction mechanism remains unknown. I aim to understand the rapid wound signal transduction in tissues that enables regeneration. The central working hypothesis is that wound signals propagate in the form of trigger waves induced by a positive feedback loop between extracellular signaling proteins and epidermal growth factor receptors. I will study the planarian, a highly-regenerative animal, as the model system and combine novel sequencing technology, functional genomics analysis, and computational modeling to quantify wound signal propagation, construct core regulatory genetic circuits, and model intercellular trigger wave dynamics. This work will help elucidate the fundamental rules that enable the rapid cell-cell communication and the collective stress response that are essential to tissue regeneration.