Julie Saugstad, Ph.D., professor of Anesthesiology and Perioperative Medicine and her lab members are interested in comparing the proteomic composition of extracellular vesicles (EVs) in cerebrospinal fluid (CSF) and plasma. This work has recently been funded by an OHSU 2020 University Shared Resources grant.
Her NIH funded studies have focused on the clinical utility of extracellular microRNAs as biomarkers for Alzheimer’s disease. However, related and important studies include how extracellular microRNAs are transported and protected from degradation in biofluids. Circulating microRNAs are carried inside of EVs, or bound to high density lipoproteins. The lab has focused their studies on EVs, as they are selectively packaged and released by all cells, and transport of molecular cargo into recipient cells can alter the phenotype of a recipient cell. Thus, the EVs contribute to specific cell-to-cell signaling, and potentially in long-distance signaling in circulating biofluids.
Dr. Saugstad’s lab has evidence that EVs in CSF are morphologically distinct from EVs in plasma. Dr. Ursula Sandau in the lab worked with Dr. Claudia Lopez at the OHSU Multiscale Microscopy Core to perform cryogenic electron microscopy, which revealed that CSF EVs are much more highly decorated than plasma EVs. This finding suggested that CSF EVs carry membrane bound and/or extracellular proteins that plasma EVs do not, and that distinct protein compositions between EVs in each biofluid ultimately may affect their role(s) in cell-to-cell signaling.
The goal of the University Shared Resources study is to carry out proteomic analysis of EVs isolated from matched CSF and plasma samples from the same individuals. The studies will be perfumed by Dr. Ashok Reddy at the OHSU Proteomics Shared Resource (PSR) and the data will be analyzed using a new Data Independent Analysis mass spectrometry technique that is currently not available in this core. Thus, this project will also enable the PSR to develop and test the method with potential to be offered as a future service.