The ability to rapidly identify functional proteins with post translation modifications (PTMs) is a crucial element in understanding cellular function. Protein PTMs have emerged in the post-genomic era critical features in regulating and diversifying protein biological activity, but identifying specific proteoforms with PTMs and understanding their function on individual proteins is currently limited by the lack of effective and accessible analytical methods. Therefore, there is a crucial need to develop a high-throughput approach to functionally characterize intact proteins and their modified proteoforms at the systems level. The overall purpose of our research program is to develop and apply new top-down and functional mass spectrometry (MS) proteomics technologies to characterize intact proteins and their modified proteoforms. This talk includes our recently developed high-throughput quantitative top-down MS platform that couples an online 2D pH RP/RPLC separation and multiplexed TMT top-down quantitation to identify and quantify low abundance intact proteins and their modified proteoforms in complex biological samples. I will also discuss our results on detecting intact autoantibody biomarkers in systemic lupus erythematosus (SLE) patient serum samples.
Si Wu, Ph.D., Assistant Professor, University of Oklahoma