Proteomics Center @ MUSC

The goals of the MUSC Cardiovascular Proteomics Center (CPC) are to develop new, generally applicable technologies for proteomic analysis and apply them to generate new discoveries in specific areas of cardiovascular research. The CPC includes seven projects and five core units. Projects 1-3 re biological studies derived from three NHLBI program projects at MUSC. Work on these projects is being initiated using a synergistic combination of contemporary two-dimensional gel electrophoresis in a new high throughput facility, a well established mass spectrometry facility, and state-of-the-art methods of biological systems analysis and machine learning, while work on new technology proceeds in parallel.

• Project 1: Application of Proteomic Analysis to Cardiovascular Research in Diastolic Heart Failure, directed by Michael R. Zile, M.D., will use proteomic analysis to study the basic underlying mechanisms of development of diastolic congestive heart failure and provide a scientifically important, clinically relevant experimental model system in rats.
• Project 2: Extracellular Matrix-Mediated Epithelial-to-Mesenchymal Transformation (EMT) Events in Cardiovascular Development and Homeostasis, is directed by Edward L. Krug, Ph.D. This project focuses on analyzing early mouse heart morphogenesis surrounding EMT remodeling events and primitive myocardial secretory dynamics that elicit EMT of endocardium and epicardium.
• Project 3: Application of Proteomic Analysis to Cardiovascular Disease Risk: Insulin Resistance Syndrome, is directed by C. Timothy Garvey, M.D. The goal of this work is to understand the mechanism of insulin resistance syndrome, by applying proteomic analyses to identify proteins that are differentially expressed or modified in human skeletal muscle as a function of insulin resistance. These biological studies applying proteomic analysis will guide the new technology development, provide a comprehensive evaluation environment for the technologies, and yield new insights in the cardiovascular issues under investigation.

There are four technology development projects.

• Project 4: Improved Methods for Separation and Identification of Proteins on Two-Dimensional Gels, directed by John M. Arthur, M.D., Ph.D., will develop methodologies to address major shortcomings of gel-based proteomics: visualization and identification of difficult proteins such as membrane and low abundance proteins and more complete determination of the components of protein complexes.
• Project 5: Microfluidic Systems for Proteomic Analysis, directed by Daniel R. Knapp, Ph.D., will develop two dimensional liquid chromatography separation systems that interface directly to mass spectrometry to enable analysis of more proteins and increase sensitivity.
• Project 6: Intact Protein-Based Proteomic Analysis, directed by Kevin L. Schey, Ph.D., entails developing a high-throughput, sensitive proteomics approach utilizing mass spectrometric identification that does not require protein digestion.
• Project 7: Computational Analysis of Proteomic Profiles, directed by Eberhard Voit, Ph.D. and Jonas Almeida, Ph.D. will develop de novo a complementary proteomics approach based on mathematical modeling, combined with time-dependent and stimulus-dependent protein profiles.

The projects will be supported by five core units.

• Core A: Gel Electrophoresis, directed by Dr. Arthur, will provide gel-based proteomic analysis for Projects 1-3.
• Core B: Mass Spectrometry, directed by Dr. Schey, will provide analytical support for Projects 1-6 and Core A, by providing protein and peptide separation and identification.
• Core C: Bioinformatics, directed by Dr. Almeida, will provide computer hardware and software for Project 7 as well as data management and analysis for the other projects. Core C will also develop and maintain the center web site.
• Core D: Machine and Electronics Shops, directed by Dr. Knapp, will provide instrument maintenance and construction for the technology development projects.
• Core E: dministration, also directed by Dr. Knapp, will provide administrative support for the CPC.

In addition to the specific cardiovascular research being pursued in the CPC, the new technology development will advance additional areas of NHLBI-related research, and research in other areas of biomedical science via application in the MUSC Proteomics Center and via dissemination to other the NHLBI Proteomics Initiative Centers as well as the research community in general.