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
Assistant Professor, MGH/Harvard Medical School · postdoc, Dana-Farber (William Kaelin lab) · PhD, MIT/Whitehead (Sabatini lab) · BS, Northeastern Univ.
Wyant Lab, MGH Cardiovascular Research Center (Boston, Massachusetts, USA) ↗ Lab lineagetrained under David M. Sabatini → ORCID0000-0002-4665-2405 ↗
Portrait: Simons Foundation (SFARI)
First author (WYA2017): SLC38A9, already known for arginine sensing, has a second job — effluxing essential amino acids like leucine out of lysosomes to activate mTORC1; pancreatic cancer cells scavenging protein by macropinocytosis depend on this efflux. Contributed to CHA2016 (CASTOR1 arginine sensor discovery).
Pivoted to oxygen sensing with Nobel laureate William Kaelin, now runs own MGH/Harvard lab studying oxygen, nutrients, mechanical stretch and electrical activity in heart/muscle growth — aimed at heart failure and cachexia.
Milestones in the Atlas
A selection, not a full bibliography: only papers that meet the Atlas inclusion criteria.
| Year | Evidence | Study |
|---|---|---|
| 2015 | M | Metabolism. Lysosomal amino acid transporter SLC38A9 signals arginine sufficiency to mTORC1 WAN2015 The lysosomal transporter SLC38A9 signals arginine sufficiency to mTORC1. |
| 2016 | M | The CASTOR Proteins Are Arginine Sensors for the mTORC1 Pathway CHA2016 Contributed to identifying CASTOR1 as the direct arginine sensor upstream of mTORC1. |
| 2017 | M | KICSTOR recruits GATOR1 to the lysosome and is necessary for nutrients to regulate mTORC1 WOL2017 KICSTOR tethers GATOR1 to the lysosome, required for nutrient control of mTORC1. |
| 2017 | M | mTORC1 Activator SLC38A9 Is Required to Efflux Essential Amino Acids from Lysosomes and Use Protein as a Nutrient WYA2017 SLC38A9 effluxes essential amino acids out of lysosomes to activate mTORC1. |
| 2018 | M | NUFIP1 is a ribosome receptor for starvation-induced ribophagy WYA2018 First author: NUFIP1 acts as a receptor that delivers ribosomes to autophagy when mTORC1 is inhibited. |
Co-authors in the Atlas 23
People with a profile here who share at least one study with Gregory A. Wyant.
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- David M. Sabatini 5 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
- Kuang Shen 3 shared studies 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
- Lynne Chantranupong 3 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
- Monther Abu-Remaileh 3 shared studies Worked out how to isolate lysosomes fast enough to measure what is inside them, and found that mTOR controls what gets out
- Rachel L. Wolfson 3 shared studies 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
- Sonia M. Scaria 2 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
- Tim Wang 2 shared studies 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
- Elizabeth D. Yuan Second author on the study showing that S6K1 phosphorylates BMAL1 to link mTOR signalling with circadian protein synthesis, and co-author on the follow-up in tuberous sclerosis models.
- Elizaveta Freinkman Chemist and mass-spectrometry specialist at the Whitehead Institute who measured metabolites for many studies of nutrient sensing and cancer metabolism, including the lysosome amino acid work behind two Atlas papers
- Choah Kim Researcher in David Sabatini's lab at the Whitehead Institute who contributed to three studies on how amino acids at the lysosome are sensed by mTORC1
- J. Wade Harper 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
- Jose M. Orozco Researcher trained in David Sabatini's laboratory at the Whitehead Institute and MIT who showed that mTORC1 senses glucose through the glycolysis metabolite DHAP
- Kendall J. Condon Ran genome-wide CRISPR screens revealing how mitochondrial stress signals to mTORC1
- 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
- Nouf N. Laqtom Cell biologist who helped develop methods to purify intact lysosomes and used them to find what the Batten disease gene CLN3 does, and who now runs a lab at KAUST on lysosome and endoplasmic reticulum defects in rare brain and metabolic diseases
- Robert A. Saxton 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
- Roberto Zoncu Showed as a postdoc that mTORC1 senses amino acids from inside the lysosome, through the v-ATPase and Ragulator. His Berkeley lab has since mapped how the Rag GTPases and the folliculin complex switch mTORC1 on, and how lysosomal cholesterol feeds into the same system
- Shuyu Wang Co-discovered SLC38A9 as a Sabatini-lab MD-PhD student, a lysosomal amino-acid transporter that signals arginine sufficiency to mTORC1
- 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
- Sze Ham Chan Researcher at the Whitehead Institute who contributed to studies of lysosome contents, nutrient sensing and cancer metabolism, mostly from David Sabatini's lab
- Walter W. Chen Co-author of the 2017 Cell paper showing that SLC38A9 releases essential amino acids from lysosomes to switch on mTORC1
- 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
- Zhi-Yang Tsun Biologist who, as first author in David Sabatini's lab, showed that the tumour suppressor folliculin is a GAP for the RagC and RagD GTPases that carry the amino acid signal to mTORC1
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