Steven P. Gygi
Mass-spectrometry scientist whose Harvard lab builds large-scale proteomics methods, including the BioPlex human protein-interaction map, and contributed proteomics to the discoveries of the CASTOR and SAMTOR nutrient sensors
Professor of Cell Biology, Harvard Medical School; faculty director, Taplin Biological Mass Spectrometry Facility and the Thermo Fisher Center for Multiplexed Proteomics · own lab, Harvard Medical School (since 2000) · postdoc, University of Washington (Ruedi Aebersold lab, from 1996) · PhD in Pharmacology and Toxicology (mass spectrometry), University of Utah
Gygi Lab, Harvard Medical School (Boston, Massachusetts, USA) ↗ Lab lineagetrained under Ruedi Aebersold → ORCID0000-0001-7626-0034 ↗
Portrait: Giovanni Armenise-Harvard Foundation
Gygi's lab supplied the identification step behind the Atlas's two BioPlex-derived nutrient-sensor papers: after Wade Harper's group immunoprecipitated a tagged 'bait' protein out of cells, it was Gygi's mass spectrometers that identified every protein sticking to it, repeated across thousands of different baits to build BioPlex. That pipeline is what put CASTOR1 (then an obscure gene, GATSL3) on a list of GATOR2-interacting proteins in 2016, and what flagged SAMTOR (then C7orf60) as a GATOR1/KICSTOR partner in 2017 — both times before anyone knew these proteins bound a nutrient at all. Screens at that scale exist mainly because Gygi's group has spent two decades making quantitative mass spectrometry faster, more sensitive, and multiplexable.
Gygi earned his PhD at the University of Utah on small-molecule mass spectrometry, then did a postdoctoral fellowship (from 1996) with Ruedi Aebersold at the University of Washington, one of the labs that founded modern quantitative proteomics. Since starting his own lab at Harvard Medical School in 2000, Gygi has been a driving force behind Tandem Mass Tag (TMT) multiplexing, which lets many samples be compared in a single mass-spec run, and more recently TMTpro, which pushed that to 16 samples at once.
He now directs two HMS core mass-spectrometry facilities — the Taplin Biological Mass Spectrometry Facility and the Thermo Fisher Center for Multiplexed Proteomics — that generate proteomic and interactome data used throughout cancer biology, neuroscience, and cell biology well beyond his own lab's projects.
Milestones in the Atlas
A selection, not a full bibliography: only papers that meet the Atlas inclusion criteria.
| Year | Evidence | Study |
|---|---|---|
| 1999 | M | Regulation of 4E-BP1 phosphorylation: a novel two-step mechanism GIN1999 4E-BP1 is phosphorylated by an ordered, priming two-step mechanism that controls its release of eIF4E. |
| 2005 | M | mTOR and S6K1 mediate assembly of the translation preinitiation complex through dynamic protein interchange and ordered phosphorylation events HOL2005 mTOR and S6K1 dynamically assemble the translation preinitiation complex on eIF3. |
| 2011 | M | Phosphoproteomic analysis identifies Grb10 as an mTORC1 substrate that negatively regulates insulin signaling YUX2011 Phosphoproteomics identify Grb10 as an mTORC1 substrate driving negative feedback on insulin/PI3K. |
| 2014 | M | The Sestrins interact with GATOR2 to negatively regulate the amino-acid-sensing pathway upstream of mTORC1 CHA2014 Sestrins bind GATOR2 to negatively regulate amino-acid signalling upstream of mTORC1. |
| 2016 | M | The CASTOR Proteins Are Arginine Sensors for the mTORC1 Pathway CHA2016 Performed the mass-spectrometry identification behind BioPlex that first showed the uncharacterized protein GATSL3 (CASTOR1) co-purifying with the GATOR2 complex. |
| 2017 | M | SAMTOR is an S-adenosylmethionine sensor for the mTORC1 pathway GU2017 Performed the mass-spectrometry profiling behind the expanded BioPlex network that identified the uncharacterized protein C7orf60 (SAMTOR) as a GATOR1/KICSTOR interactor. |
Co-authors in the Atlas 22
People with a profile here who share at least one study with Steven P. Gygi.
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- David M. Sabatini 3 shared studies Identified mTOR (as RAFT1) in 1994. His lab then mapped much of the machinery around it: raptor and rictor at the core of mTORC1 and mTORC2, the Rag–Ragulator system that docks mTORC1 on the lysosome, and the sensors that detect leucine, arginine and SAM
- Robert A. Saxton 3 shared studies Solved, as a Sabatini-lab graduate student, the structures of the leucine sensor Sestrin2 and the arginine sensor CASTOR1, showing how each one grips its amino acid. He also co-wrote a widely cited 2017 review of mTOR signalling with David Sabatini
- Sonia M. Scaria 3 shared studies Contributed, as an MIT undergraduate in the Sabatini lab, to the discovery of CASTOR1 as the arginine sensor and SAMTOR as the SAM sensor of the mTORC1 pathway
- J. Wade Harper 2 shared studies Co-discovered the F-box motif that links substrates to SCF ubiquitin ligases, and co-leads with Steven Gygi the BioPlex protein-interaction map, which contributed to the discoveries of the CASTOR and SAMTOR nutrient sensors
- John Blenis 2 shared studies Showed early on that rapamycin blocks S6 kinase, then worked out how mTORC1 drives cell growth through its two main translation targets, S6K1 and 4E-BP1. His lab also found, in parallel with the Sabatini lab, that mTORC1 phosphorylates Grb10, a feedback brake on insulin signalling
- Jose M. Orozco 2 shared studies Researcher trained in David Sabatini's laboratory at the Whitehead Institute and MIT who showed that mTORC1 senses glucose through the glycolysis metabolite DHAP
- Lynne Chantranupong 2 shared studies Showed as a Sabatini-lab graduate student that the Sestrins act through GATOR2 to regulate amino-acid signalling to mTORC1. She then discovered the CASTOR proteins, the cell's arginine sensors for the pathway
- Anne-Claude Gingras Showed in 1999 that mTOR phosphorylates 4E-BP1 in a priming two-step mechanism, and now leads work on interaction proteomics (including BioID) that maps how cells read signals such as mTORC1
- Eric Spooner Manager of the Whitehead Institute's Proteomics Core Facility, whose mass spectrometry work identified proteins in complexes for many Whitehead studies, including two on amino acid sensing upstream of mTORC1
- Grace Y. Liu Wrote with David Sabatini a major 2020 review of mTOR in nutrition, growth and ageing, and in the Sabatini lab studied how mTORC1 senses nutrients such as serine
- Gregory A. Wyant Showed that the lysosomal protein SLC38A9 exports leucine and other essential amino acids out of the lysosome, letting cells grow on proteins they have taken up and broken down there
- Kendall J. Condon Ran genome-wide CRISPR screens revealing how mitochondrial stress signals to mTORC1
- Kuang Shen Solved, as a Sabatini-lab postdoc, cryo-EM structures of GATOR1 and of the FLCN–FNIP2–Rag–Ragulator complex, two switches that set mTORC1 activity. His UMass Chan lab studies the structural basis of nutrient sensing
- Lewis C. Cantley Co-discovered PI3K, the pathway that feeds into mTOR from growth factors
- Liron Bar-Peled Showed as a Sabatini-lab graduate student that Ragulator switches the Rag GTPases on, acting as their GEF. He also discovered GATOR1 and GATOR2; GATOR1 switches the Rags off and its genes are mutated in some cancers
- Marina K. Holz Cell biologist who, as a postdoc with John Blenis, showed how mTOR and S6K1 trade places on eIF3 to start protein synthesis, and who now studies mTOR in breast cancer and the rare lung disease LAM at New York Medical College
- Nahum Sonenberg Co-discovered the mRNA cap-binding protein eIF4E and the 4E-BP proteins that restrain it, and showed how mTOR releases this brake to control protein synthesis
- Rachel L. Wolfson Identified Sestrin2 as the direct leucine sensor of the mTORC1 pathway as a Sabatini-lab MD-PhD student. She also co-discovered KICSTOR, the complex that recruits GATOR1 to the lysosome
- Robert T. Abraham Co-discovered the mammalian target of rapamycin in 1995, giving it the name mTOR, and showed that it directly phosphorylates the translation repressor 4E-BP1 (PHAS-I)
- Tim Wang Co-developed genome-wide CRISPR screening in human cells (reported in parallel by Feng Zhang's lab) as a graduate student with David Sabatini and Eric Lander, and contributed to studies showing that the 4E-BPs mediate mTORC1's control of translation and that CASTOR1 senses arginine
- Xin Gu Cell biologist who discovered SAMTOR, the sensor that lets mTORC1 read the methyl donor SAM, as a PhD student at MIT, and who now leads a lab at Dana-Farber and Harvard Medical School studying ubiquitin-independent protein destruction by the midnolin-proteasome pathway
- Yonghao Yu Used phosphoproteomics to show that mTORC1 phosphorylates and stabilises Grb10, which then acts as a feedback brake on insulin and IGF-1 signalling
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