OXIDATIVE POST-TRANSLATIONAL MODIFICATIONS IN CARDIOVASCULAR DISEASE

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The research of the NHLBI-sponsored Cardiovasculaar Proteomics Center focuses on the oxidative post-translational modifications that occur in conjunction with cardiovascular disease. The Core laboratory develops appropriate methods and provides capLC-QTOF analysis of peptides in digests of 2D-gel separated or multistage HPLC purified proteins. In conjunction with the Resource, MALDI-TOF MS, LTQ-Orbitrap MS/MS and FTMS mass spectral analyses are also carried out. Software to assist in data processing and interpretation is being generated in the Center. A novel VC-MALDI cryogenic Fourier transform mass spectrometer with a 14-T magnet is being constructed to enable high throughput, high performance analysis of proteolysis mixtures from biological sources, and efficient, accurate determination of their post-translational modifications. Basic and clinical investigators, primarily located at BUSM and HMS, are using proteomic approaches to investigate the effects of oxidative stress on cell cultures, tissues and whole organisms. During this reporting year, in addition to numerous oral and poster meeting presentations, two methods papers that involved Resource collaboration, one on bioinformatics and one on novel hydrophobic fluorous derivatives, were published, in addition to applications papers that explored FTMS methods, and collaborations yielded papers on platelet stimulation pathways and oxidative modification of sirtuin.