My group has long-standing, extensive expertise and experience in mass spectrometry, proteomics and systems biology, especially focused on sequencing, identification and study of unknown proteins, and the detection, assignment and site-specific dynamics of posttranslational modifications of proteins, particularly OGlcNAcylation, phosphorylation, acetylation, methylation and ubiquitinylation. Over many years we have collaborated with the neurobiological community extensively, including structural characterization of the GPI membrane anchor of the prion protein, structure of the lysyl oxidase co-factor, identification and PTM regulation of proteins in the retrograde signaling complexes in damaged axons, the O-GlcNAc/phosphorylation dynamics at the murine synapse, identification of new proteins involved in the Nodes of Ranvier, etc.
In addition to the work in proteomics and epigenetics above, we have focused significant effort on other studies concerning the architecture of protein complexes and machines for which angstrom resolution structural information has not yet been tractable. For example we have developed a new lysine-lysine cross-linking strategy based on chemical reductive amination that provides comprehensive sequence and cross-link site assignments using electron transfer dissociation (ETD). This information provides accurate distance constraints that complement cryoEM and computer modeling efforts. In parallel software algorithms and scoring strategies have been developed that greatly facilitates the assignment of cross-linked peptides in general. Very recently we have initiated a thrust into development and application of methodology to measure protein complexes directly in the gas phase using a newly acquired high mass Orbitrap Exactive instrument (m/z < 22,000). This effort will complement our long-standing work on chemical cross-linking of protein complexes and machines.
Finally, we have developed a general suite of programs and software tools required for processing large scale mass spectral data sets (HCD, ETD, etc) and stable isotopic labeling experiments (SILAC, iTRAQ, etc) called Protein Prospector.
July 1, 1985 - May 31, 2023 - UCSF Liver Center , Co-Investigator . Sponsor: NIH, Sponsor Award ID: P30DK026743
August 1, 2002 - April 30, 2020 - Genetic Biochemical Studies of Plant Steroid Signaling , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01GM066258
September 30, 1987 - March 31, 2017 - Toxic Substances in the Environment , Co-Investigator . Sponsor: NIH, Sponsor Award ID: P42ES004705
March 15, 1997 - May 31, 2016 - Bio-Organic Biomedical Mass Spectrometry Resource , Principal Investigator . Sponsor: NIH, Sponsor Award ID: P41GM103481
University of Rhode Island, Kingston, RI, B.S. 1959, Chemistry
MIT, Cambridge, MA, Ph.D., 1962, Chemistry, Physics