Oliver's mTOR Atlas Evidence Platform
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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

Associate Professor, Program in Molecular Medicine, UMass Chan Medical School · PhD in Chemistry, California Institute of Technology · postdoc, David Sabatini lab, Whitehead Institute/MIT

Shen Lab, UMass Chan (Worcester, Massachusetts, USA) ↗ Bluesky@shenk0128.bsky.social ↗

Kuang Shen Portrait: Shen Lab, UMass Chan Medical School

Kuang Shen trained as a structural biologist in David Sabatini's lab, applying cryo-electron microscopy to the amino-acid-sensing machinery that switches mTORC1 on and off at the lysosome.

He solved structures of GATOR1 and the GATOR1-Rag GTPases complex, the GAP machinery that turns mTORC1 off in the absence of amino acids, and of the FLCN-FNIP2-Rag-Ragulator complex, revealing at near-atomic detail how these complexes physically engage the Rag GTPases to control their nucleotide state. He now runs his own structural-biology lab at UMass Chan Medical School, studying the mTORC1 pathway with cryo-EM, single-molecule and enzyme-kinetic methods.

The timeline below follows Shen's contributions gathered in this Atlas.

Milestones in the Atlas

A selection, not a full bibliography: only papers that meet the Atlas inclusion criteria.

YearEvidenceStudy
2014 M A diverse array of cancer-associated MTOR mutations are hyperactivating and can predict rapamycin sensitivity GRA2014 A spectrum of cancer-associated MTOR mutations are hyperactivating and predict rapamycin sensitivity.
2015 M Sestrin2 is a leucine sensor for the mTORC1 pathway WOL2015 Sestrin2 is a direct leucine sensor whose leucine binding releases GATOR2 to activate mTORC1.
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 Co-authors the discovery that the CASTOR proteins are arginine sensors for the mTORC1 pathway.
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.
2018 M Ragulator and SLC38A9 activate the Rag GTPases through noncanonical GEF mechanisms SHE2018B Ragulator and SLC38A9 each act as an unusual guanine-nucleotide exchange factor on the Rag heterodimer, and together they push it into its active state. Ragulator triggers GTP release from RagC, which unlocks the inactive configuration; arginine-bound SLC38A9 converts RagA from the GDP- to the GTP-loaded state. Boundary: purified proteins and cultured human cells. This is the biochemistry of the switch, not a measurement in tissue.
2018 M Architecture of the human GATOR1 and GATOR1-Rag GTPases complexes SHE2018 Solves the architecture of the human GATOR1 and GATOR1-Rag GTPases complexes, the GAP machinery that switches mTORC1 off.
2019 M Cryo-EM Structure of the Human FLCN-FNIP2-Rag-Ragulator Complex SHE2019 Solves the cryo-EM structure of the human FLCN-FNIP2-Rag-Ragulator complex.

Co-authors in the Atlas 25

People with a profile here who share at least one study with Kuang Shen.

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  • David M. Sabatini 8 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
  • Lynne Chantranupong 5 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
  • Gregory A. Wyant 3 shared studies 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
  • 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 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
  • Kendall J. Condon 2 shared studies Ran genome-wide CRISPR screens revealing how mitochondrial stress signals to mTORC1
  • Rick K. Huang 2 shared studies Cryo-electron microscopy specialist who, at the HHMI Janelia Research Campus, helped solve the 2018 and 2019 structures of the protein machines that pass amino acid signals to mTORC1
  • Robert A. Saxton 2 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
  • 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
  • Brian C. Grabiner Catalogued cancer-associated MTOR mutations and showed that many of them hyperactivate the kinase and can predict sensitivity to rapamycin; he also contributed to the discovery of GATOR1
  • Edward J. Brignole Research scientist who directs the cryo-electron microscopy facility at MIT.nano and whose cryo-EM work helped solve the structures of GATOR1, GATOR2 and Raptor docked on the Rag GTPases for the Sabatini lab
  • 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.
  • 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
  • Kacper B. Rogala Solved the near-atomic cryo-EM structure that shows how mTORC1 physically docks at the lysosome by reading the Rag GTPases
  • Kivanç Birsoy Cancer metabolism researcher who trained with Jeffrey Friedman and David Sabatini and now heads the Laboratory of Metabolic Regulation and Genetics at The Rockefeller University, using genetic screens to find how cancer cells rewire their metabolism
  • 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
  • Max L. Valenstein First author of the cryo-EM structures of GATOR2, the hub that tells mTORC1 whether amino acids are present, alone and bound to the sensors Sestrin2 and CASTOR1
  • Monther Abu-Remaileh Worked out how to isolate lysosomes fast enough to measure what is inside them, and found that mTOR controls what gets out
  • 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
  • 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

Every researcher with a profile →

On the programme

Meetings in the Atlas calendar where Kuang Shen is listed among the speakers or organisers.

All meetings in the calendar →

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