Shuyu Wang
Co-discovered SLC38A9 as a Sabatini-lab MD-PhD student, a lysosomal amino-acid transporter that signals arginine sufficiency to mTORC1
Postdoctoral fellow, UCSF Department of Psychiatry and Behavioral Sciences (Manoli Lab) · MD–PhD, Harvard/MIT MD-PhD Program (2018; PhD in Biology, MIT, thesis “Studies of amino acid sensing by the mTORC1 pathway”, David Sabatini lab, Whitehead Institute)
Manoli Lab, UCSF (San Francisco, California, USA) ↗
Portrait: UCSF Dept. of Psychiatry and Behavioral Sciences
Shuyu Wang was part of David Sabatini's lab at the Whitehead Institute during the effort to work out exactly how amino acids are sensed inside the lysosome, the organelle where mTORC1 sits when nutrients are plentiful.
In 2011 she was among the authors of the paper showing that lysosomal amino acids activate mTORC1 through an “inside-out” mechanism — amino acids inside the lysosome are signalled outward through the v-ATPase, which engages Ragulator and the Rag GTPases to recruit mTORC1 to the lysosomal surface. That paper suggested that amino acid signalling to mTORC1 begins inside the lysosome itself, not just in the cytoplasm.
She then led one of the 2015 papers (published alongside a study from Giulio Superti-Furga's group) that identified a missing piece of that inside-out mechanism: SLC38A9, a lysosomal membrane transporter that physically senses arginine inside the lysosome and signals its sufficiency to mTORC1. SLC38A9 turned out to be a direct physical link between the raw presence of an amino acid and the Rag GTPase switch that turns mTORC1 on.
Wang did this work as an MD–PhD student in the Harvard/MIT program; her MIT thesis (2018) was titled “Studies of amino acid sensing by the mTORC1 pathway.” She then trained in psychiatry at UCSF and is now a postdoctoral research fellow there in Devanand Manoli's lab, studying the neural circuits of social behaviour — a long way from the lysosome, but the SLC38A9 paper remains one of the defining results in nutrient sensing (sources: Harvard/MIT MD-PhD alumni listing; UCSF Psychiatry).
Milestones in the Atlas
A selection, not a full bibliography: only papers that meet the Atlas inclusion criteria.
| Year | Evidence | Study |
|---|---|---|
| 2011 | M | mTORC1 senses lysosomal amino acids through an inside-out mechanism that requires the vacuolar H(+)-ATPase ZON2011 Shows lysosomal amino acids activate mTORC1 through an inside-out mechanism, suggesting that amino acid signalling begins inside the lysosome. |
| 2015 | M | Metabolism. Lysosomal amino acid transporter SLC38A9 signals arginine sufficiency to mTORC1 WAN2015 Identifies SLC38A9 as a lysosomal amino acid transporter that interacts with the Rag GTPases and Ragulator and signals arginine sufficiency to mTORC1. |
Co-authors in the Atlas 13
People with a profile here who share at least one study with Shuyu Wang.
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- David M. Sabatini 2 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
- Liron Bar-Peled 2 shared studies 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
- Roberto Zoncu 2 shared studies 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
- Alejo Efeyan Showed that the Rag GTPases, which relay amino-acid signals to mTORC1, are a life-or-death switch for newborn mice surviving the fast before their first feeding
- 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.
- 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
- 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
- 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
- Lynne Chantranupong 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
- 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
- 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
- Yasemin Sancak Showed as a Sabatini-lab graduate student, in parallel with Kun-Liang Guan's lab, that the Rag GTPases relay amino-acid signals to mTORC1, and that Ragulator anchors them to the lysosome where mTORC1 is switched on. She also identified PRAS40 as an insulin-regulated inhibitor of mTORC1
- 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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