Thomas Wales

Sponsor: NIH/DFCI

 Targeting SHP-1 through a newfound metabolite-regulated cysteine activation site

This new project is focused on chemical manipulation and characterization of SHP-1 based on recent insights, gained in large part from the development of mass spectrometry approaches to map small molecule covalent interactions proteome-wide done in the Chouchani laboratory. My research group will apply hydrogen-deuterium exchange (HDX) mass spectrometry (MS) to investigate conformational changes of SHP-1 upon binding to itaconate and itaconate- mimetics to ascertain if SHP-1 activation leads to conformational rearrangement and then determine where those rearrangements take place within SHP-1. These HDX MS studies will provide solution-based measurements that will complement the X-ray crystallography studies of the same system.