Kevin L. Schey
Professor of Biochemistry, Vanderbilt University
Director of Core Facilities, Mass Spectrometry Research Center
- : k.schey@vanderbilt.edu
- : 615-936-6861
- :
9126D MRB III
465 21st Avenue South
Nashville, Tennessee - 37232 - : Lab Website
I am interested in the analysis of the molecular components of EVs, both proteins and lipids, through proteomics and lipidomics methods. I am interested in urine EVs as sources of disease biomarkers as well as in EVs from ocular tissues as conduits of cell-to-cell communication.
Research Description: The Schey lab is interested in both method/instrument development in proteomics analysis as well as in applications of state-of-the-art proteomics technologies in the study of development and disease. Method development/technology projects include methods for integral membrane protein analysis, tandem mass spectrometry of intact proteins (top-down proteomics), spatially-resolved proteomics analysis, and quantitative proteomics. The major area of application is human lens protein modifications and protein-protein interactions. Other areas of interest are: proteomics analysis of heart valve development, and invertebrate (shrimp and oyster) innate immunity. Integral membrane proteins play key roles in signaling, transport, and adhesion, yet they remain difficult to analyze using conventional proteomics methods.
Our lab has developed methods to analyze integral membrane proteins and membrane associated proteins including their modifications. In addition, we have developed methods for membrane proteome analysis. Currently we are developing methods for spatially-resolved studies (see below), for tissue imaging of membrane proteins, and for examining the membrane protein phosphoproteome. Standard proteomics analyses typically require tryptic digestion of the protein sample followed by LC/MS/MS analysis of the peptides in order to identify and quantitate the proteins present in the sample. This bottom-up approach relies on inferring protein level information from peptide level measurements. Top-down analysis involves analysis of the intact proteins for identification but requires sophisticated technologies and software.
We have developed a method for top-down proteomics analysis in a MALDI TOF-TOF platform and generated a new software application for the interpretation of resulting data. Spatially-resolved proteomics represents a critically important area of development that takes advantage of recent advances in instrumental sensitivity. The ability to examine region-specific changes in a proteome has wide applicability in both development and disease processes. Two approaches are being developed in our lab to address this issue: 1) laser capture microsdissection (LCM) coupled with shotgun proteomics analysis and 2) MALDI tissue imaging. We have combined our membrane protein analysis protocols with LCM capture to examine region-specific changes in the ocular lens membrane proteome. Also, we have developed new sample preparation methods to allow MALDI imaging of membrane proteins. The MALDI imaging method is being applied to lens aging, chick and mouse heart development, shrimp viral infection, brain changes in addiction, and lung infection. Our long-standing project on ocular lens membrane proteins is focused on how these proteins change as lens cells differentiate and as they age. Since the proteins in the lens core are as old as the individual, the lens serves as a model tissue to study protein aging. Age- and cataract-specific modifications have been identified and regional changes in the membrane proteome are being examined. Functional consequences of lens protein modification are also being examined with confocal microscopic, molecular biology, and spectroscopic methods.