Research
Our research group has the overarching goal of catalyzing evolution in the rapidly developing field of proteomics and to use these technologies to address fundamental problems in developmental biology.
The epigenotype of pluripotency. This research is based on the following hypothesis: human ES cells are distinguished from their somatic cell counterparts by unique epigenotypes. The new technology created by our laboratory has allowed for the first high fidelity examination of human ES cell histone modification patterns. Ongoing aims in the laboratory include the global characterization and quantification of the full repertoire of PTM patterns within the core histone tails of human ES cells relative to human control cells. And, using potent differentiating agents, we aim to determine the changes to those histone codes upon lineage commitment.
Elucidation of the cellular signaling pathways that commit hES cells to exit the pluripotent state. Here we use our novel PTM-friendly sequencing technologies to reveal the phosphorylation cascades that set the irreversible differentiation process in motion. To date we have identified 3,819 unique sites of protein phosphorylation from human ES cells. We have now begun to carefully monitor these sites to determine which branches of the FGF signaling pathway are active in human ES cells and which proteins/networks are phosphorylated in response to TPA. This work is funded through a private donation with co-investigator J. Thomson.
Sequential ion/ion reactions for large peptide and whole protein sequence analysis. This project aims to develop a suite of ion/ion reaction chemistries, and to automate their use in a novel MS system. This work is funded by the NIH (RO1 GM080148) and by Thermo Fisher Scientific through a sponsored research agreement.
Gas-phase coordination chemistry for rapid, robust whole protein sequencing. This project seeks to develop small molecule anions that covalently bind to selected sites of a gas-phase protein cation (e.g., selected amino acids). The bound anionic reagents will then serve as scaffolds to harbor site-specific cleavage, with enzyme-like specificity. This project has been funded by the Beckman Young Investigator Program.
The development of novel computational algorithms for protein sequence identification. Here we aim to develop new algorithms to determine the sequence of a peptide or protein directly from a tandem mass spectrum. This work is performed jointly with Mathematics Professor Gheorghe Craciun.