Research Abstract

Research in my lab, starting in 2000 at Harvard Medical School, centers on the proteome-wide measurement and characterization of proteins by high performance mass spectrometry. One of the most dramatic developments in biological research is the shift from the analysis of single genes and proteins to the comprehensive analysis of biological systems and pathways. This shift is a consequence of the development of automated, high-throughput genomic technologies and their application to sequence complete genomes and to measure gene expression on a genome-wide scale. Currently, no comparably powerful technology is available for the analysis of biological systems on the protein level. However, proteins are the principal functional units of the living world—the molecules which carry out most catalytic, structural, and regulatory functions inside cells. A complete model of a biological process cannot be established without knowledge of the involved players and a mechanistic characterization of their functional roles. Nowhere is this more evident than in the Ubiquitin System where the substrates for >500 E3 ubiquitin ligases and ~100 deubiquitinases remain largely unexplored. I believe that sample multiplexing using isobaric tagging reagents has tremendous potential to address this gap. Up to 16 cellular conditions can be combined using TMT reagents allowing for the inclusion of complex experimental designs with replicates, dose response, rescue, and time series data. Finally, a 16plex TMT experiment represents a closed system where all measurements across the N proteins x 16 conditions matrix are available with basically no missing values. I am committed to the development of technologies and computational techniques for the rapid, sensitive, quantitative and multiplexed analysis of protein expression profiles from diverse cellular settings.