Biophysical Characterization of EVPs and other Macromolecular Nanoparticles

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Liquid biopsies are part of this emerging frontier in biomedical research. This frontier is of interest to all areas of biology and medicine and is of particular interest to the cancer research community. Circulating tumor cells (CTCs) and cell-free nucleic acids (cfNAs) are two types of liquid biopsies where clear progress has been made in the past decade towards understanding these CTC and cfNA tumor-related and systems-based biological information. Systematic, accurate, and reproducible studies of sub-micron extracellular vesicles (EVs) and other nanoscale macromolecular assemblies (collectively referred to hereafter as extracellular vesicles and particles, or EVPs) are difficult to perform due to a lack of robust and reliable tools for correctly measuring these submicron and nanoscale materials. CCR's mission is to improve the lives of all cancer patients by solving important, challenging, and neglected problems in cancer research and patient care. The Translational Nanobiology Section's particular expertise, perspective, collaborations, and vision within CCR is building bridges to span the existing gaps between basic biophysical and metrological first principles, advanced molecular multi-omics strategies, and clinical translational investigation in order to develop systematic, robust, and accurate ways to study EVPs tumor-, immune-, and stromal-/vascular- EVP compositions as they relate to tumor progression and treatment response in our cancer patients. Although the specific focus of my lab pertains most immediately to cancer and cancer-related immunobiology, we intend for our work to be a general asset to the biomedical research community. As such, my Section is committed to sharing our tools for general research use, so that they can accelerate studies in other diseases as well. The ultimate goal of my program is to leverage the information content in EVPs to interrogate biological systems in a systematic manner, that is, by identification and characterization of specific sub-sets of EVPs to 'read' the status of compartments represented by those sub-sets. The purpose of Projects 1 and 2 in the Translational Nanobiology Lab is to develop and demonstrate the use of new tools for the field to use that will enable us to monitor tumor, immune, and vascular/stromal systems in a manner that we hope will enable us to perform blood tests to detect relevant changes in those systems early in the course of radiation or other therapies, and we hope that this will more broadly serve as a foundation for enabling selectively (system-specific) adaptive treatment strategies in the future. Project 1 is focused on spanning the gap in available tools and knowledge to accurately characterize the liquid biopsy components, EVPs and their cargo, for Project 2.