My research group aims to catalyze evolution in the rapidly developing field of proteomics and to use these technologies to address fundamental problems in developmental biology. With an emphasis on ion chemistry and instrumentation, we develop and apply new, enabling mass spectrometry-based (MS) proteomic technologies. Past successes in instrumentation include: the coupling electron-transfer dissociation to an Orbitrap mass analyzer, the addition of a high resolution mass filter over an ion trap to increase throughput and isolation fidelity, the development of both collision- and photon-activated methods to boost ETD efficiency (ETcaD and AI-ETD, respectively), and the use of ETD reagents for spectral calibration to eliminate mass accuracy drift. Such cutting-edge tools allow us to examine, for example, the molecular events that commit human embryonic stem cells (hES cells) to exit the pluripotent state with unprecedented chemical detail and sensitivity. Here we are focused on intracellular signaling, the epigenetic regulation of pluripotency, and interpreting and monitoring epigenetic codes. Coupled with instrumentation, new methodology is a vital component in accomplishing our overarching goal. In this vein, we have led the way in using intelligent data acquisition logic (Decision Tree) ETD with collision-activated dissociation (CAD), using ETD with isobaric tagging for protein quantification, and using ETD with various proteases other than trypsin to increase proteome coverage. Finally, our informatics team works on unique spectra pre-processing routines, an ETD-specific search algorithm called zCore (now commercially available), and an open platform for ETD spectral processing (COMPASS).
Research projects include: (1) instrumentation development, (2) data analysis software design, (3) fundamental ion chemistry studies, and (4) biological applications: global identification of protein post-translational modification (specifically phosphorylation), quantitative analysis of protein phosphorylation (i.e., comparative analysis of two cellular states), and cancer biomarker discovery, among others.