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David M. Sabatini

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

IOCB Prague · Howard Hughes Medical Institute (2008–2021) · Whitehead Institute & MIT (1997–2021) · Born 1968, New York, USA

Sabatini Group, IOCB Prague (Prague, Czech Republic) ↗ Lab lineagetrained under Solomon H. Snyder → ORCID0000-0002-1446-7256 ↗

David M. Sabatini Portrait: Ceal Capistrano/Whitehead Institute for Biomedical Research

David Sabatini grew up in a family of scientists — his father is a well-known cell biologist — and trained as an MD–PhD at Johns Hopkins in the laboratory of Solomon Snyder. As a graduate student he became fascinated by rapamycin, a drug found in the soil of Easter Island that could stop cells from growing. Nobody knew what it actually hit inside mammalian cells. In 1994 Sabatini answered that question: using rapamycin bound to its partner protein FKBP12 as 'bait', he fished a giant protein out of rat brain and named it RAFT1, the protein now called mTOR. That discovery opened the mammalian side of the field.

In 1997, still in his twenties, he started his own lab at the Whitehead Institute in Cambridge. Over the next two decades the Sabatini lab identified many core parts of the mTOR machine: the two complexes mTORC1 and mTORC2, the Rag GTPases and Ragulator that dock mTORC1 onto the lysosome, and — most strikingly — the actual protein sensors (Sestrin2, CASTOR1, SLC38A9, SAMTOR) that let a cell literally taste individual amino acids such as leucine and arginine. Together this work explained how our cells decide, moment to moment, whether there is enough food to grow.

His discoveries earned major honours including the Louisa Gross Horwitz Prize and the BBVA Frontiers of Knowledge Award. In 2021–2022 he left MIT and the Whitehead Institute. Since late 2023 he has led a laboratory at the Institute of Organic Chemistry and Biochemistry (IOCB) in Prague. The timeline below traces his scientific path through the studies collected in this Atlas.

Milestones in the Atlas

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

YearEvidenceStudy
1994 M RAFT1: a mammalian protein that binds to FKBP12 in a rapamycin-dependent fashion and is homologous to yeast TORs SAB1994 Three years after yeast TOR, Sabatini purifies the Target Of Rapamycin (RAFT1/mTOR) from rat brain, proposing it as the direct target of FKBP12-rapamycin and a mammalian homolog of the yeast TOR proteins.
1998 M RAFT1 phosphorylation of the translational regulators p70 S6 kinase and 4E-BP1 BUR1998 RAFT1/mTOR directly phosphorylates p70 S6K (Thr389) and 4E-BP1, the two central translational effectors.
2002 M mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery KIM2002 Defines mTOR Complex 1 by discovering raptor (reported in parallel by the Yonezawa and Avruch labs), the partner protein that makes mTOR sensitive to nutrients.
2003 M GbetaL, a positive regulator of the rapamycin-sensitive pathway required for the nutrient-sensitive interaction between raptor and mTOR KIM2003 Discovered mLST8 (GbetaL), the third core subunit that clamps onto mTOR's kinase domain and stabilizes the complex. It fine-tunes how tightly Raptor holds mTOR in response to nutrients - a small but essential cog that later turned out to be especially critical for the mTORC2 complex.
2003 M TOS motif-mediated raptor binding regulates 4E-BP1 multisite phosphorylation and function SCH2003 The TOS motif mediates raptor binding and controls multisite 4E-BP1 phosphorylation by mTORC1.
2004 M Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton SAR2004 Discovers mTOR Complex 2 (via rictor, in parallel with Michael Hall's lab), a second, rapamycin-insensitive mTOR machine that controls the cytoskeleton.
2005 M Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex SAR2005 The rictor-mTOR complex (mTORC2) directly phosphorylates Akt/PKB on Ser473, regulating cell survival.
2006 M Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB SAR2006 The molecular explanation for rapamycin's dark side. Short-term rapamycin only hits mTORC1, but prolonged treatment can also inhibit the assembly of NEW mTORC2 in susceptible cell types, reducing mTORC2 abundance and cutting Akt signaling over time. The wording matters: this is prevention of new assembly, not the dismantling of complexes already built, and the response depends on cell context and length of exposure. This is the mechanistic root of the insulin-resistance side effect later shown in mice (see Lamming 2012) - crucial for anyone dosing rapamycin for longevity.
2006 M mSin1 is necessary for Akt/PKB phosphorylation, and its isoforms define three distinct mTORC2s FRI2006 mSin1 is required for mTORC2 assembly and Akt Ser473 phosphorylation; isoforms define distinct complexes.
2006 M Ablation in mice of the mTORC components raptor, rictor, or mLST8 reveals that mTORC2 is required for signaling to Akt-FOXO and PKCalpha, but not S6K1 GUE2006 The foundational genetic 'dissection' of the two complexes in living mice. Deleting Raptor was lethal early (mTORC1 essential); deleting Rictor or mLST8 selectively knocked out mTORC2 signaling to Akt and PKCalpha but spared S6K1. This cleanly assigned jobs to each complex and showed mLST8 is an mTORC2-specific requirement in mice.
2007 R Defining the role of mTOR in cancer GUE2007 Comprehensive review arguing mTOR signaling is commonly deregulated in human cancers, laying out the rationale for rapalog trials in oncology.
2007 M PRAS40 is an insulin-regulated inhibitor of the mTORC1 protein kinase SAN2007 Identified PRAS40 as the missing insulin-controlled brake INSIDE mTORC1. When insulin is absent PRAS40 clamps the complex shut; insulin makes Akt phosphorylate PRAS40, releasing the brake so Rheb can fully switch mTORC1 on. Explained how hormone signals set the exact strength of mTORC1 activity.
2008 M The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1 SAN2008 Shows, in parallel with Kun-Liang Guan's lab, that the Rag GTPases are the switch that relays the amino-acid signal to mTORC1.
2009 A mTOR complex 2 is required for the development of prostate cancer induced by Pten loss in mice GUE2009 mTORC2 is required for prostate cancer driven by Pten loss in mice.
2009 M An ATP-competitive mammalian target of rapamycin inhibitor reveals rapamycin-resistant functions of mTORC1 THO2009 Dropped a bombshell: rapamycin does NOT fully block mTORC1. Using Torin1 (which jams the active site directly), the authors showed rapamycin leaves important mTORC1 jobs running - notably 4E-BP1 phosphorylation and autophagy suppression. This reframed a decade of rapamycin experiments and launched the search for complete inhibitors.
2009 M DEPTOR is an mTOR inhibitor frequently overexpressed in multiple myeloma cells and required for their survival PET2009 Identified DEPTOR as a built-in brake on BOTH mTOR complexes. The twist: in some multiple myelomas DEPTOR is overexpressed, which by relieving a feedback loop actually keeps pro-survival Akt signaling ON - a neat example of how an 'inhibitor' can be co-opted by cancer.
2010 M Structure of the human mTOR complex I and its implications for rapamycin inhibition YIP2010 Co-authors the cryo-EM structure of human mTORC1, an obligate dimer that FKBP12-rapamycin gradually breaks apart in vitro.
2010 M Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids SAN2010 Ragulator docks mTORC1 onto the surface of the lysosome — pinpointing where nutrient sensing physically happens.
2010 R mTOR: from growth signal integration to cancer, diabetes and ageing ZON2010 Authoritative review of mTOR from growth-signal integration to disease.
2010 M mTORC1 controls fasting-induced ketogenesis and its modulation by ageing SEN2010 mTORC1 controls fasting-induced hepatic ketogenesis via PPARalpha, and this is blunted with age.
2011 M The mTOR-regulated phosphoproteome reveals a mechanism of mTORC1-mediated inhibition of growth factor signaling HSU2011 mTOR-dependent phosphoproteomics reveal Grb10 as a substrate mediating feedback inhibition of PI3K.
2011 M mTORC1 senses lysosomal amino acids through an inside-out mechanism that requires the vacuolar H(+)-ATPase ZON2011 Showed amino acid sensing starts INSIDE the lysosome: amino acids accumulate in the lumen and the v-ATPase relays that signal outward ('inside-out') to Ragulator-Rag. A surprising twist on where the cell measures its nutrient status.
2011 M mTOR complex 1 regulates lipin 1 localization to control the SREBP pathway PET2011 mTORC1 controls lipin-1 nuclear localization to regulate SREBP and lipid synthesis.
2012 A Regulation of mTORC1 by the Rag GTPases is necessary for neonatal autophagy and survival EFE2012 Rag-GTPase control of mTORC1 is essential for neonatal autophagy and survival to fasting.
2012 M Ragulator is a GEF for the rag GTPases that signal amino acid levels to mTORC1 BAR2012 Ragulator was reported as a guanine-nucleotide exchange factor for RagA/B on the lysosome; later work places Ragulator's exchange activity on RagC and assigns RagA GTP loading to SLC38A9, so the tethering role is the better-established one.
2012 R mTOR signaling in growth control and disease LAP2012 The classic 2012 Cell review that became the standard reference for mTOR signaling. Comprehensive yet readable synthesis of how mTOR integrates environmental cues to control growth, and how its deregulation drives cancer, obesity, diabetes and neurodegeneration. A perfect companion to the newer 2020 review.
2012 A Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity LAM2012 Chronic rapamycin (about 2 mg/kg a day, close to the lifespan-extending dose) made mice glucose intolerant and insulin resistant. A clamp test placed the problem in the liver, which kept making glucose, while muscle and fat took up glucose normally. Removing mTORC1 from the liver did not cause this. Rapamycin did break up mTORC2 (it separated mTOR from Rictor) in liver, fat and muscle, and deleting Rictor in the liver alone reproduced the glucose problem. In the genetic part, female mice with one working copy each of mTOR and mLST8 had about 50% less mTORC1 signalling in the liver, normal mTORC2 signalling and normal glucose tolerance, and lived 14.4% longer on average (p = 0.046). Males did not. Boundary: mouse drug and genetics work, not people, and the lifespan gain is female-only. It supports separating the two effects, but the paper does not test a drug that blocks mTORC1 without touching mTORC2.
2012 M A lysosome-to-nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB SET2012 A lysosome-to-nucleus mechanism uses mTOR-dependent TFEB phosphorylation to sense lysosomal state.
2012 A TOR signaling and rapamycin influence longevity by regulating SKN-1/Nrf and DAF-16/FoxO ROB2012 In C. elegans, genetic TORC1 inhibition extends lifespan through SKN-1/Nrf and DAF-16/FoxO, whereas rapamycin's lifespan effect requires SKN-1 but not DAF-16, apparently because it also hits TORC2.
2012 M mTORC1 in the Paneth cell niche couples intestinal stem-cell function to calorie intake YIL2012 Senior author: calorie restriction expands mouse intestinal stem cells by lowering mTORC1 in the Paneth cells of their niche, not in the stem cells themselves, and rapamycin reproduces the effect.
2012 M A unifying model for mTORC1-mediated regulation of mRNA translation THO2012 Used ribosome profiling with the complete inhibitor Torin1 to address a long-standing debate: in these cells, mTORC1's translational control runs largely through the 4E-BP family acting on a specific class of mRNAs (TOP motifs). Losing just the 4E-BPs makes translation of TOP mRNAs resistant to mTOR inhibition - naming them the master effectors.
2013 M The folliculin tumor suppressor is a GAP for the RagC/D GTPases that signal amino acid levels to mTORC1 TSU2013 FLCN-FNIP is a GAP for RagC/D; GDP-bound RagC/D is required for the Rag heterodimer to bind mTORC1, promoting its lysosomal recruitment and activation by amino acids.
2013 M A Tumor suppressor complex with GAP activity for the Rag GTPases that signal amino acid sufficiency to mTORC1 BAR2013 Found the OFF switch for amino acid signaling: the GATOR1 complex is a GAP that shuts the Rag GTPases (and thus mTORC1) down when amino acids run low, while GATOR2 opposes it. GATOR1 genes are mutated in cancers, making those tumors 'blind' to starvation and hypersensitive to rapamycin.
2013 M mTORC1 phosphorylation sites encode their sensitivity to starvation and rapamycin KAN2013 Senior author of the finding that mTORC1 phosphorylation sites encode their own sensitivity to rapamycin and starvation, so one activity level can produce different output profiles.
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.
2014 H Activating mTOR mutations in a patient with an extraordinary response on a phase I trial of everolimus and pazopanib WAG2014 Two concurrent activating MTOR mutations are implicated in an extraordinary clinical response to rapalog therapy. Single-patient observation: hypothesis-generating, not evidence of a general response predictor.
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 Identifies Sestrin2 as a direct leucine sensor for the mTORC1 pathway.
2015 M Structural basis for leucine sensing by the Sestrin2-mTORC1 pathway SAX2015 Solves the crystal structure of Sestrin2 bound to leucine, revealing the molecular pocket that lets it act as mTORC1's dedicated leucine sensor.
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 Mechanism of arginine sensing by CASTOR1 upstream of mTORC1 SAX2016 CASTOR1 is a direct arginine sensor upstream of mTORC1; structure reveals the arginine-binding mechanism.
2016 M The CASTOR Proteins Are Arginine Sensors for the mTORC1 Pathway CHA2016 Identified CASTOR1 as the direct arginine sensor: when arginine binds CASTOR1, it lets go of GATOR2, switching mTORC1 on. Together with Sestrin2 (leucine) this built the picture of mTORC1 as a cell that literally tastes individual amino acids.
2017 R mTOR Signaling in Growth, Metabolism, and Disease SAX2017 Comprehensive synthesis of mTORC1/mTORC2 signaling, growth regulation, metabolism, and disease relevance.
2017 R Twenty-five years of mTOR: Uncovering the link from nutrients to growth SAB2017 Sabatini's own 25-year retrospective on mTOR: uncovering the link from nutrients to growth.
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 (e.g. leucine) from lysosomes to activate mTORC1.
2017 R The Dawn of the Age of Amino Acid Sensors for the mTORC1 Pathway WOLF2017 Review of the newly discovered amino-acid sensors feeding into mTORC1.
2017 M SAMTOR is an S-adenosylmethionine sensor for the mTORC1 pathway GU2017 Extended nutrient sensing beyond amino acids to METABOLITES: SAMTOR reads S-adenosylmethionine (SAM), the cell's methyl-donor currency, linking methionine and one-carbon metabolism to mTORC1. Relevant to why methionine restriction affects aging.
2018 M NUFIP1 is a ribosome receptor for starvation-induced ribophagy WYA2018 Senior author of the finding that NUFIP1 is a ribosome receptor for starvation-induced ribophagy, triggered by mTORC1 inhibition.
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 Cryo-EM structures of GATOR1 and GATOR1-Rag complexes reveal GAP and inhibitory-clamp mechanisms.
2019 M Cryo-EM Structure of the Human FLCN-FNIP2-Rag-Ragulator Complex SHE2019 Cryo-EM structure of the human FLCN-FNIP2-Rag-Ragulator complex.
2019 M Architecture of human Rag GTPase heterodimers and their complex with mTORC1 ANA2019 Structures of Rag GTPase heterodimers with mTORC1 explain nucleotide-state-dependent recruitment.
2019 M Structural basis for the docking of mTORC1 on the lysosomal surface ROG2019 3.2-angstrom cryo-EM structure of Raptor bound to Rag-Ragulator, showing how Raptor reads out the nutrient-dependent nucleotide state of the Rag GTPases: one part of Raptor senses RagA's nucleotide state, a separate 'claw' senses RagC's, and both have to be in the correct nutrient-signalling combination before Raptor is allowed to dock. Mutating the contact points blocks mTORC1 from reaching the lysosome and inhibits its signalling, which is the functional evidence behind the structural claim. Combined with a separate structure of mTORC1 bound to its activator Rheb, the paper builds a model of the complete, active mTORC1 sitting on the lysosome. Boundary: cryo-EM of a complex reconstituted from purified human proteins, not a live-cell measurement.
2020 R mTOR at the nexus of nutrition, growth, ageing and disease LIU2020 The flagship modern review of the whole field, from Sabatini's own lab (Nature Reviews Molecular Cell Biology). Maps 25+ years of mTOR biology - how it senses nutrients, controls growth and autophagy, and goes wrong in cancer, neurodegeneration, metabolic disease and aging. The single best orientation document for the entire Atlas.
2021 M Genome-wide CRISPR screens reveal multitiered mechanisms through which mTORC1 senses mitochondrial dysfunction CON2021 Genome-wide CRISPR screens reveal AMPK and HRI relay mitochondrial dysfunction to mTORC1.
2022 M Structure of the nutrient-sensing hub GATOR2 VAL2022 Cryo-EM structure of human GATOR2: a 1.1 MDa, two-fold symmetric cage built on an octagonal scaffold decorated with eight pairs of WD40 beta-propellers, and a map of where Sestrin2 and CASTOR1 dock. It substantially advances the GATOR2 side of the sensor module, though how GATOR2 inhibits GATOR1 is still not fully settled.

Co-authors in the Atlas 82

People with a profile here who share at least one study with David M. Sabatini.

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  • Lynne Chantranupong 12 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
  • Kuang Shen 8 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
  • Liron Bar-Peled 8 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
  • Rachel L. Wolfson 8 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
  • Robert A. Saxton 8 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
  • Roberto Zoncu 8 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
  • Carson C. Thoreen 7 shared studies Used Torin1, one of the first ATP-competitive mTOR inhibitors, to reveal functions of mTORC1 that rapamycin cannot block. He then showed that mTORC1 controls translation of mRNAs for the protein-making machinery mainly through the 4E-BP proteins
  • David A. Guertin 7 shared studies Built the mouse genetics that defined mTORC2's biological roles
  • Seong A. Kang 7 shared studies Contributed to the Sabatini-lab studies that identified PRAS40 and DEPTOR, two of the cell's own mTOR inhibitors, and to the first characterisation of the mTOR inhibitor Torin1
  • Timothy R. Peterson 6 shared studies Discovered DEPTOR, an inhibitor that binds mTOR in both complexes and is overexpressed in some multiple myelomas. He also showed that mTORC1 controls fat synthesis by regulating where the enzyme lipin 1 sits in the cell, and through it the SREBP pathway
  • Dos D. Sarbassov 5 shared studies Discovered rictor as a Sabatini-lab postdoc, in parallel with Michael Hall's lab, defining mTOR Complex 2, and showed that this complex is the long-sought kinase that phosphorylates Akt on serine 473. He also found that prolonged rapamycin treatment can block mTORC2 assembly
  • Gregory A. Wyant 5 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
  • Siraj M. Ali 5 shared studies Worked in the Sabatini lab on the papers that discovered raptor, mLST8 and rictor, and on the finding that the rictor-mTOR complex phosphorylates Akt. He later moved into cancer genomics and clinical diagnostics
  • Sonia M. Scaria 5 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 5 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
  • Yasemin Sancak 5 shared studies 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
  • Hediye Erdjument-Bromage 4 shared studies Ran the mass-spectrometry analyses in Paul Tempst's lab at Memorial Sloan Kettering that identified the unknown proteins in the raptor, mLST8 and rictor purifications, and contributed the same approach to work on how ERK inactivates TSC2
  • Jose M. Orozco 4 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
  • Kacper B. Rogala 4 shared studies Solved the near-atomic cryo-EM structure that shows how mTORC1 physically docks at the lysosome by reading the Rag GTPases
  • Kendall J. Condon 4 shared studies Ran genome-wide CRISPR screens revealing how mitochondrial stress signals to mTORC1
  • Monther Abu-Remaileh 4 shared studies Worked out how to isolate lysosomes fast enough to measure what is inside them, and found that mTOR controls what gets out
  • Nathanael S. Gray 4 shared studies Medicinal chemist whose lab designed Torin1, an ATP-competitive mTOR inhibitor that blocks functions of mTORC1 that rapamycin misses. His lab is also known for covalent kinase inhibitors and targeted protein degraders
  • Paul Tempst 4 shared studies Developed mass-spectrometry methods for identifying proteins from tiny samples, and led the Memorial Sloan Kettering proteomics laboratory that identified the unknown partners of mTOR in the raptor, mLST8 and rictor purifications
  • Xin Gu 4 shared studies 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
  • Alejo Efeyan 3 shared studies 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
  • Brian C. Grabiner 3 shared studies 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
  • Do-Hyung Kim 3 shared studies Co-discovered raptor, the defining partner of mTOR in mTORC1, and then mLST8 (GbetaL) as a Sabatini-lab postdoc. His Minnesota lab identified PRAS40 as an insulin-regulated link to mTORC1 and studies how mTORC1 controls autophagy
  • Dudley W. Lamming 3 shared studies Showed as a postdoc that rapamycin's harm to glucose metabolism comes largely from its effect on mTORC2, while the lifespan benefit tracks mTORC1. His Wisconsin lab studies intermittent rapamycin dosing and how restricting dietary protein or single amino acids affects metabolism and ageing
  • Edward J. Brignole 3 shared studies 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
  • Mathieu Laplante 3 shared studies Co-wrote with David Sabatini one of the field's most cited reviews of mTOR in growth and disease, and his Laval lab studies how mTORC1 and DEPTOR control fat tissue and metabolism
  • Robert R. Latek 3 shared studies Bioinformatics scientist at the Whitehead Institute who worked on the Sabatini-lab papers that described raptor, mLST8 (GbetaL) and rictor (raptor and rictor were reported in parallel by other labs), the core partners of mTOR in its two complexes
  • Shomit Sengupta 3 shared studies Showed that mTORC1 controls whether the liver makes ketone bodies during fasting, and now leads biology for drug discovery at a metabolic-disease biotech
  • Steven P. Gygi 3 shared studies 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
  • Andrew L. Markhard 2 shared studies Contributed, as a Sabatini-lab researcher, to the discovery that Ragulator docks mTORC1 on the lysosome, and now studies metabolite signals that tell the body it has eaten
  • Eric Spooner 2 shared studies 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 2 shared studies 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
  • Choah Kim 2 shared studies 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 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
  • Kathleen Ottina 2 shared studies Researcher in David Sabatini's lab at the Whitehead Institute and HHMI at MIT who contributed to studies of the GATOR1 amino acid off-switch, mTORC1 feedback on growth-factor signalling, and cancer drug resistance
  • Kevin E. Knockenhauer 2 shared studies Structural biologist trained in Thomas Schwartz's MIT lab who helped solve the amino acid sensor structures of Sestrin2 and CASTOR1, and who later moved to drug discovery at Accent Therapeutics
  • Kivanç Birsoy 2 shared studies 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
  • Max L. Valenstein 2 shared studies 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
  • Michael B. Yaffe 2 shared studies Cancer biologist and physician-scientist known for working out how phosphorylation creates binding sites on proteins, including the 14-3-3 family of phosphoserine/threonine-binding proteins, and how kinases choose their targets.
  • Nouf N. Laqtom 2 shared studies 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
  • Peggy P. Hsu 2 shared studies Identified, in parallel with Yonghao Yu's group, Grb10 as an mTORC1 substrate that feeds back to dampen insulin and growth-factor signalling, and now studies the earliest steps of lung cancer as a physician-scientist
  • 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 Lindquist 2 shared studies Researcher in David Sabatini's group at the Whitehead Institute who ran large image-based RNAi screens for regulators of TORC1 signaling and helped build the CellProfiler image-analysis software
  • Shuyu Wang 2 shared studies Co-discovered SLC38A9 as a Sabatini-lab MD-PhD student, a lysosomal amino-acid transporter that signals arginine sufficiency to mTORC1
  • Thomas U. Schwartz 2 shared studies MIT structural biologist who studies how molecules pass across the nuclear envelope, and whose crystallography lab helped solve the leucine and arginine sensor structures upstream of mTORC1
  • Zhi-Yang Tsun 2 shared studies 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
  • Adam B. Salmon Biologist of aging at UT Health San Antonio whose work in this Atlas spans rapamycin in mice and in common marmosets. He is a co-author on the Interventions Testing Program reports from the San Antonio site and on the marmoset rapamycin studies on blood markers, epigenetic age and the salivary gland
  • Alex Berndt Protein scientist in Roger Williams' group at the MRC Laboratory of Molecular Biology who helped solve structures of PI3K enzymes and of mTOR and its partners
  • Andrea Ballabio Discovered that the transcription factor TFEB is a master switch for building lysosomes (SAR2009) and for autophagy. His lab was one of the groups that showed in 2012 that mTORC1 keeps TFEB out of the nucleus from the lysosome surface, and later (2020) that constitutive TFEB activation drives the kidney disease of Birt-Hogg-Dubé syndrome
  • Arlan Richardson Studies how rapamycin slows ageing in mice, including the broad changes it causes in the liver, and co-authored early studies showing that rapamycin protects memory in Alzheimer's-model mice
  • Benjamin E. Turk Kinase biochemist who studies how protein kinases choose their substrates; co-author on the discovery that AMPK phosphorylates raptor and on the study showing that mTORC1 sites differ in intrinsic substrate quality.
  • Calvin K. Yip Structural biologist who uses electron microscopy to study large protein machines; as a postdoc at Harvard Medical School he determined a cryo-EM structure of human mTORC1, and his lab now studies the autophagy machinery.
  • Carmine Settembre Showed, as first author in Andrea Ballabio's lab, that TFEB drives autophagy as well as lysosome production, and, in parallel with other groups, that mTORC1 phosphorylates TFEB at the lysosome to keep this program switched off when nutrients are plentiful
  • Diane C. Fingar Studies how mTORC1 and mTORC2 are regulated, especially through site-specific phosphorylation
  • Diego L. Medina Cell biologist at the Telethon Institute of Genetics and Medicine in Naples who showed how TFEB, the master switch for lysosome genes, is controlled by calcium released from lysosomes, and who works on lysosomal storage diseases
  • 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
  • Christopher Johnson Biophysicist who built and ran the Biophysics Facility at the MRC Laboratory of Molecular Biology, measuring how proteins fold, bind and change shape for dozens of research groups
  • John Blenis 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
  • Jonathan E. Rosenberg A bladder and urothelial cancer oncologist whose clinical trial work includes the case of an exceptional responder to everolimus with activating MTOR mutations.
  • Joseph A. Baur Biologist of aging at the University of Pennsylvania whose lab showed that rapamycin's harm to glucose control comes from mTORC2 loss and studies how NAD levels shape health
  • Madhanagopal Anandapadamanaban Structural biologist at the MRC Laboratory of Molecular Biology who solved the structure of the human Rag GTPases bound to mTORC1, showing how amino acids bring mTORC1 to the lysosome
  • Maria A Frias Cancer biologist who did her doctoral research on mTORC2 in David Sabatini's lab and now teaches biology at St. Francis College in Brooklyn, while continuing work with David Foster on how the lipid phosphatidic acid controls mTOR
  • Matthew Meyerson Cancer geneticist whose group has helped identify key genes mutated in lung cancer, and who contributed the cancer-genome analysis to the discovery that GATOR1 is a tumour suppressor acting on mTORC1
  • Michael E. Pacold Radiation oncologist and chemical biologist at NYU Langone who studies the metabolism of brain tumours, and a co-author of the Sabatini lab's structure of the leucine sensor Sestrin2
  • Nada Y. Kalaany Studies how a tumour's metabolism depends on the metabolic state of the whole body, and hunts for nutrient dependencies that can be turned into treatments
  • Nikhil Wagle Medical oncologist and cancer genomics researcher at Dana-Farber who studies why some patients respond exceptionally well to targeted drugs, including a patient whose tumour carried two activating MTOR mutations
  • Ömer H. Yilmaz Pathologist and stem-cell biologist who studies how diet and nutrient sensing control intestinal stem cells; as a postdoc with David Sabatini he showed that calorie restriction acts on the stem-cell niche through mTORC1 in Paneth cells
  • Pranav V. Lalgudi Co-author of the cryo-EM structures of GATOR2, the nutrient-sensing hub of mTORC1, in 2022 and of GATOR2 bound to Sestrin2 and CASTOR1 in 2025
  • Qingsong Liu Medicinal chemist in Nathanael Gray's lab who helped discover Torin1, an ATP-competitive mTOR inhibitor, and later built an independent kinase-inhibitor drug-discovery program in China
  • Roger L. Williams Solved structures showing how the Rag GTPases bind mTORC1 and how TOR forms a dimer, working at the MRC Laboratory of Molecular Biology
  • Stacey Robida-Stubbs Researcher in Keith Blackwell's worm lab at the Joslin Diabetes Center who showed that TOR inhibition and rapamycin extend C. elegans lifespan through the protective factors SKN-1/Nrf and DAF-16/FoxO
  • Stefanie S. Schalm Cell biologist who, in John Blenis's lab, showed that the TOS motif lets raptor grab 4E-BP1 so mTORC1 can phosphorylate it, and who later moved into cancer drug discovery in the biotech industry
  • 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
  • T. Keith Blackwell Geneticist who uses the worm C. elegans to study how the SKN-1/Nrf stress-response factor, insulin signaling and TOR shape stress resistance and lifespan.
  • Tuong Huynh Research associate at Baylor College of Medicine in Houston and co-author on a long run of papers from Andrea Ballabio's group on TFEB, the master switch for lysosome and autophagy genes, including the work that tied TFEB to mTOR, starvation and fat metabolism
  • W. Michael Kuehl Physician-scientist who spent decades working out the genetic and molecular biology of multiple myeloma and its precursor condition MGUS.
  • Walter W. Chen Co-author of the 2017 Cell paper showing that SLC38A9 releases essential amino acids from lysosomes to switch on mTORC1

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