The overall goal of this Research Career Scientist award is to foster the nominee’s ongoing research program that is focused on the study of extracellular vesicles (EVs) and their extracellular RNA (exRNA) cargo as biomarkers and effectors of human health and disease including among Veterans. Through participation in a national NIH-funded consortium research program, the nominee is working to develop novel methods to study EVs and other carriers of exRNA for biomarker development projects. The nominee also recently reported the first evidence of intercellular signaling between macrophage EVs and hematopoietic progenitor cells to control the process of systemic and vascular inflammation and atherosclerosis cardiovascular disease. Ongoing funding from a VA Merit grant is supporting the nominee’s goal of exploring the role of circulating EVs isolated from Veterans treated for advanced vascular disease as biomarkers and contributors to disease progression including via microRNA cargo. Experiments in the lab will also test if EVs produced from anti- inflammatory macrophages can serve to control inflammation and atherosclerosis in diabetic rodent models. Furthermore, funding from a VA Invention-based Supplement Award will support pre-clinical studies testing such anti-inflammatory EVs as therapeutics to control cardiac inflammation and heart failure in a rodent model system developed and patented for the VA by the nominee. Findings from these studies could provide much needed new therapeutics in the form of EV-biologics to treat inflammatory diseases including in the cardiovascular system that is a major healthcare need among the Veteran patient population. The nominee’s internationally recognized program on EV biology has led to new collaborative research projects with VA clinician investigators at the local and offsite stations. This includes a collaborative project to test EVs produced by cultured stem cells as therapeutic mediators of skeletal muscle regeneration. Such studies have been proposed in a VA Merit grant proposal with the nominee serving as co-Investigator, which is being revised for a resubmission. The nominee is also engaged in collaborative studies with VA clinician investigators to develop biomarkers of adverse outcomes of surgical procedures used to treat advanced vascular disease among Veterans. Finally, projects proposed by the nominee through grants pending at the Department of VA and the NIH make use of EV technology and expertise developed by the nominee to address the COVID19 disease crisis. This includes by making use of new methods of EV detection in biofluids to develop biomarkers for clinical outcomes of COVID19 disease. It also includes developing new forms of engineered EVs designed to serve in improving host immune response against SARS-CoV-2 viral infection as well as to control lung inflammation. Together, the award will serve to sustain the nominee’s momentum to developing a first-in-class research program centered o...