ABSTRACT This diversity supplement project is embedded in the Aim 1 studies of the parent grant R01- DE031299. The objective of Aim1 is to establish efficacy of the immune capture-based strategy for TEX and NTEX isolation from plasma of HNSCC patients and determine the potential of these sEV subsets to serve as biomarkers of cancer and immune competence, respectively. The aim of this research experience plan for the applicant is to utilize the available experimental design, extensive preliminary results, unique reagents and methods we have developed to optimize the immune capture strategy for tumor-derived sEV (TEX) from HNSCC plasma and harmonize its application to large-scale experiments with sEV from various cohorts of patients. While harmonizing the immune capture methodology for TEX and NTEX, the applicant will have an opportunity to acquire experience in a broad spectrum of methods and technologies, including vesicle preparation for mass spectrometry, that are required for assessments of nanovesicles characteristics and functions. The Program Leader will serve as a Mentor, with the Program Co-leaders providing medical or epidemiology advice as needed. The applicant will perform sEV isolation from body fluids, assess sEV morphology, molecular content and functions and will receive training in various microscopic, biochemical and functional technologies necessary for the vesicle characterization. The applicant will also perform in vivo experiments, delivering TEX and NTEX to mice. He will participate in data analysis, results interpretation and presentation and will interact with biostatistics and bioinformatics experts. The program is designed to prepare the applicant for an independent research career in oral cancer biology.