Prof. Steven Gygi

Harvard Medical School


Steven Gygi, Ph.D., received his Ph.D. from the University of Utah in Pharmacology and Toxicology performing small molecule mass spectrometry. He went on to pursue postdoctoral work with Ruedi Aebersold at the University of Washington in 1996.  A revolution in biological mass spectrometry was occurring which allowed for the measurement of protein expression levels, and a new field, Proteomics, was born.  In 2000, Dr. Gygi moved to Harvard Medical School and joined the Department of Cell Biology.  Currently, he is the faculty director of two MS core facilities (Taplin Biological MS Facility, and the Thermo Fisher Center for Multiplexed Proteomics).

Research in the Gygi lab centers around developing and applying new technologies in the field of mass spectrometry-based proteomics.  These include the systematic and proteome-wide measurements of many protein properties including their expression levels, modification states, structure, localization, function, and interactions.  For example, the Gygi lab, together with the Harper lab at HMS, is creating a genome-scale map of the protein-protein interaction landscape in cells (termed BioPlex).  In addition, sample multiplexing techniques like Tandem Mass Tags (TMT) are being improved to allow up to 32 proteomics samples to be analyzed simultaneously using high-resolution mass spectrometry.  One growing application area for TMT is in fragment-based drug discovery where entire libraries can be profiled for reactivity towards thousands of cysteines in cells.


Invited SpeakerSample multiplexing combined with profiling covalent cysteine libraries for FBDD

Electrophilic compound libraries contain hundreds to thousands of members which can often target cysteine residues in target proteins.  Sample multiplexing can be used to increase throughput and a new 32plex TMT reagent set is now available, making the profiling of entire libraries possible.  In this presentation, I will show examples of cysteine profiling for electrophilic libraries in both targeted and untargeted assays.  For untargeted assay, more than 20,000 cysteines can be examined for compound binding in a single run.  In addition, we used the 32plex reagent set to quickly profile all compounds in our library containing a cyclic sulfone which has been shown to bind to the pocket of Pin1 and to cysteine 113.  We identified pocket features that facilitate fragment binding.