The main focus of our lab is the study of proteins and their roles in cellular signaling events. While great strides in understanding intracellular signal transduction have been made in recent years by using molecular biological techniques, we feel that a more complete understanding of the dynamics of intracellular decision-making processes can be gained only by studying the proteins directly, or even changes in small molecule metabolites in response to changes in proteins. We use mass spectrometry as the main tool for our studies because of the wide variety of information about protein structure it can provide while requiring only small amounts of protein for analysis. The majority of our work is conducted in collaboration with neuroscientists at NYU or other universities through our NINDS-funded Mass Spectrometry Core for Neuroscience.
One goal of our research is to identify proteins that interact with each other during specific signaling events. Our lab has a special interest in the study of signal transduction in neurons, especially the neurotrophin signaling pathways. The basic strategy for these experiments is to isolate protein complexes by immunoprecipitation or affinity chromatography, cleave the protein with a specific protease such as trypsin, then determining the amino acid sequences of the peptides by quadrupole-Orbitrap tandem mass spectrometry. The masses and tandem mass spectra (containing peptide sequence information) of the peptides are then used to search genome databases to identify the proteins. To get more information about the relative amounts of each protein that participate in signaling complexes in the stimulated and nonstimulated states, we use stable isotope coding methods (for example, stable isotope labeling in cell culture, or SILAC) or tandem mass tags. In this way we can identify and quantify thousands of proteins in a single experiment.
Another focus of our work is to identify posttranslational modifications on proteins and their roles in cell signaling. In the past we have focused on modifications of single proteins, but more recently we have performed global analyses in which we identify and measure changes in tens of thousands of phosphorylation sites, or thousands of ubiquitination sites, in response to addition of growth factor to cells or disease status.
Professor, Department of Cell Biology
Director - Proteomics Core
PhD from Johns Hopkins University
Journal of proteome research. 2017 Mar 03; 16(3):1121-1132
eLife. 2017 Feb 6; 6:?-?
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