SUMMARY Synopsis: This is a K01 application by Dr. Luis Escobar, researcher on zoonotic infectious diseases. Escobar’s project Integrative Spatial Epidemiology Study of Wildlife Rabies Spillover will combine spatial modeling with large epidemiological, genomic, and ecological data to investigate pathogen spillover from wildlife to humans and livestock. Candidate: PI Escobar, DVM/MSc/PhD, is a tenure-track Assistant Professor at Virginia Tech, with prior postdoctoral training at SUNY Upstate Medical University and the University of Minnesota and a strong record of scientific achievements. This application has three training objectives to strengthen Escobar’s research as an independent investigator: (1) Training in bioinformatics; (2) Integrate bioinformatics with spatial epidemiology; and (3) Gaining skills in laboratory management and research proposal development to transition to career independence. Mentors: Prof. X.J. Meng, with a solid history of NIH funding, outstanding expertise in bioinformatics, and at the applicant’s institution, will serve as Primary Mentor. Four additional mentors (Drs. Z. Tu, W. Hopkins, S. VandeWoude, A.T. Peterson) will provide complementary expertise and will assess Escobar’s progress towards career independence. Research: Emergent infectious diseases, such as Ebola, Nipah, and COVID-19, have been linked to pathogen spillover from bats to other species. A gap in knowledge exists in the fundamental ecology of pathogen spillover transmission (i.e., Where does it occur and why?), which limits understanding of previous epidemics and capacities to prevent disease emergence. This project will study pathogen spillover from bats to humans and livestock using rabies from the common vampire bat (Desmodus rotundus), a well-documented system of a virus that frequently spills from D. rotundus bats over to other species. While D. rotundus-rabies is restricted to Latin America, it is rapidly expanding towards the United States (US) for unknown reasons. The central hypothesis is that D. rotundus-rabies spillover does not occur randomly in the geography but follows specific biodiversity and habitat patterns, which can be used to predict where pathogen spillover will occur. Aim 1 will determine the role of habitat and virus lineage on rabies-spillover to humans and livestock across Latin America. Aim 2 will identify effect of biodiversity composition on rabies virus spillover transmission. Aim 3 will investigate genomic, geographic, and environmental factors shaping the spread of rabies virus. This hypothesis-driven project has conceptual and technological innovations and combines the expertise of PI Escobar and mentors to illuminate ecological drivers of rabies spillover. Findings will offer new mechanistic insights to explain and anticipate pathogen spillover. As such, this K01 application will facilitate Escobar’ s transition towards research independence and offers exciting discoveries on the ecology of spillover transmission, aligned with the NIH mission to seek fundamental knowledge about the nature of living systems to enhance human health.

PROJECT NARRATIVE The proposed research on rabies spillover from wildlife to humans and livestock is relevant to public health because pathogen spillover (i) can generate highly infectious emerging zoonotic diseases, (ii) can cause human and economic losses, and (iii) generally originates from wildlife. Little is known about ecological drivers of rabies spillover (and pathogen spillover more generally), including why some geographic areas are infected while others are not. This proposal represents a novel theoretical and analytical approach to understand pathogen spillover transmission, which is directly relevant to NIH’s mission to seek fundamental knowledge of the nature of living systems and application of that knowledge to enhance human health.