More than 70% of emerging diseases are vector-borne or zoonotic in origin. The One Health Initiative recognizes the link between ecosystems, humans, domestic animals and wildlife in an effort to integrate human and veterinary medicine with ecology. This abstract is a call for collaborators across the LTER network to assist in developing a One Health Initiative that aims to identify ecological drivers of cross-species disease transmission in a changing environment. By comparing transmission dynamics of infectious diseases across LTER sites that span the urban to rural spectrum, we will better understand ecological and sociological drivers and thresholds that regulate infectious diseases. By way of example, we took a One Health approach to investigate rabies transmission in the northern Flint Hills around Konza Prairie Biological Station. We evaluated public health records, veterinary records, and evaluated habitat use of the reservoir host, to create a model of current rabies transmission throughout the ecosystem, from wildlife through domestic animals to humans. We also created a forecasted model of transmission after 50 years of fire suppression and woody encroachment. Although humans were exposed most frequently to rabies via domestic cats and livestock, this exposure was a result of secondary exposure from the primary rabies reservoir, striped skunks. Striped skunks responded positively to exurbanization and fire suppression, which in turn increased the risk of human exposure. Vaccination of domestic cats, public education, and controlled burning reduced disease transmission of rabies in our model. By expanding surveillance to include a broader spectrum of diseases and a broader spectrum of environments and anthropogenic disturbances, we may better understand how diseases emerge and are maintained in a changing environment. Contact: Samantha Wisely, wisely@ksu.edu