Oliver's mTOR Atlas Evidence Platform
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Brendan D. Manning

Was among the groups that in 2002 identified TSC2 as a direct target of Akt (MAN2002), linking insulin and PI3K signalling to mTORC1, and later found TBC1D7 as the third subunit of the TSC complex. His lab has shown how mTORC1 turns growth signals into the synthesis of lipids and nucleotides

Harvard T.H. Chan School of Public Health & Harvard Medical School · postdoc with Lewis Cantley · PhD, Yale

Manning Lab, Harvard Chan School (Boston, Massachusetts, USA) ↗ Lab lineagetrained under Lewis C. Cantley → Bluesky@bdmanning.bsky.social ↗ ORCID0000-0003-3895-5956 ↗

Brendan D. Manning

Brendan Manning studied at UMass Amherst and Yale, then joined Lewis Cantley's lab at Harvard for his postdoctoral work. There he made a defining discovery, reported in parallel by other groups: the tuberous sclerosis (TSC) tumour-suppressor proteins are the missing link between the PI3K–AKT pathway — which is switched on in most human cancers — and the mTOR growth machine (MAN2002, TEE2002). This tied a major cancer-signalling network directly to a nutrient sensor.

Running his own lab at Harvard, Manning has shown how mTORC1 acts as a 'metabolic rheostat', switching on production of the building blocks a growing cell needs — nucleotides, lipids and proteins — and how drugs such as metformin act on this network. His work explains how cell growth and metabolism are wired together in health and in cancer.

Manning has received an Outstanding Investigator Award from the National Cancer Institute. The milestones below trace his contributions in this Atlas.

Milestones in the Atlas

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

YearEvidenceStudy
2002 M Tuberous sclerosis complex-1 and -2 gene products function together to inhibit mammalian target of rapamycin (mTOR)-mediated downstream signaling TEE2002 Co-author: TSC1 and TSC2 act together to inhibit mTOR signalling to S6K1 and 4E-BP1 (cells).
2002 M Identification of the tuberous sclerosis complex-2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinase/akt pathway MAN2002 First author: identifies the TSC2 protein tuberin as a direct Akt substrate, linking PI3K–Akt growth-factor signalling to S6K1 and mTORC1 output (cells).
2003 M Tuberous sclerosis complex gene products, Tuberin and Hamartin, control mTOR signaling by acting as a GTPase-activating protein complex toward Rheb TEE2003 TSC1-TSC2 acts as a GTPase-activating protein (GAP) for Rheb; when TSC is inactive, Rheb accumulates in its active GTP-bound form and activates mTOR signalling.
2004 M Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/TSC2 tumor suppressor complex BRU2004 Hypoxia inhibits mTOR via REDD1-dependent activation of the TSC1/2 complex.
2004 M The LKB1 tumor suppressor negatively regulates mTOR signaling SHAW2004 Co-author: LKB1 is needed to turn mTOR signalling down when ATP falls, through AMPK and TSC2 (cells and mice).
2010 M Activation of a metabolic gene regulatory network downstream of mTOR complex 1 DUV2010 Senior author: active mTORC1 switches on glycolysis, the pentose phosphate pathway and lipid synthesis through HIF1α and SREBP1/2 (cells).
2012 M TBC1D7 is a third subunit of the TSC1-TSC2 complex upstream of mTORC1 DIB2012 Completes the TSC complex by identifying TBC1D7 as its third subunit — the master off-switch upstream of mTORC1.
2013 M Stimulation of de novo pyrimidine synthesis by growth signaling through mTOR and S6K1 BEN2013 mTORC1-S6K1 stimulates de novo pyrimidine synthesis by phosphorylating CAD.
2013 R Signal integration by mTORC1 coordinates nutrient input with biosynthetic output DIB2013 Review: mTORC1 integrates nutrient input with biosynthetic output.
2014 M Spatial control of the TSC complex integrates insulin and nutrient regulation of mTORC1 at the lysosome MEN2014 Shows insulin moves the TSC complex off the lysosome, releasing the brake on mTORC1.
2016 M mTORC1 induces purine synthesis through control of the mitochondrial tetrahydrofolate cycle BEN2016 Reveals how mTORC1 drives purine synthesis through the mitochondrial folate cycle.
2017 M mTORC1 Couples Nucleotide Synthesis to Nucleotide Demand Resulting in a Targetable Metabolic Vulnerability VAL2017 Hyperactive mTORC1 couples nucleotide synthesis to demand; imbalance drives replication stress in these cells.
2017 M Metformin Inhibits Hepatic mTORC1 Signaling via Dose-Dependent Mechanisms Involving AMPK and the TSC Complex HOW2017 Pinned down HOW the diabetes drug metformin - a major longevity candidate - actually reaches mTOR. In the liver, metformin lowers cellular energy, and at low doses this shuts down mTORC1 specifically through AMPK and the TSC complex. Direct mechanistic bridge between a widely-used drug, energy sensing, and the mTOR pathway.
2019 R Molecular logic of mTORC1 signalling as a metabolic rheostat VAL2019 Frames mTORC1 signalling as a metabolic rheostat coupling growth signals to biosynthesis.
2019 R The PI3K-AKT network at the interface of oncogenic signalling and cancer metabolism HOX2019 Review of the PI3K-AKT-mTOR network at the interface of oncogenic signalling and metabolism.
2026 A Dietary protein governs the role of insulin signaling in the postprandial regulation of hepatic mTORC1. KAL2026 Senior author showing hepatic mTORC1's postprandial activation requires dietary protein, not just insulin — AKT-TSC2 phosphorylation drives insulin's effect but is dispensable for feeding-induced activation.
2026 A Feeding-Induced Muscle mTORC1 Signaling Regulates Postprandial Protein Synthesis and Endurance but Not Muscle Size LAP2026 Using a mouse model expressing an AKT-nonphosphorylatable TSC2 mutant specifically in skeletal muscle, the Manning lab genetically separated feeding-induced from contraction-induced mTORC1 activation. AKT-mediated TSC2 phosphorylation is required for feeding (but not contraction) to activate muscle mTORC1 and drive postprandial protein synthesis — yet mice lacking this feeding-induced signal have normal muscle mass and myofiber size, and instead show improved maximal endurance capacity with a modest rise in mitochondrial content. The finding dissociates mTORC1's role in postprandial anabolism from its role in maintaining steady-state muscle mass, and is a directly relevant data point for whether the pattern/source of mTORC1 activation (feeding vs. mechanical) — not just its average level — shapes downstream outcomes.

Co-authors in the Atlas 27

People with a profile here who share at least one study with Brendan D. Manning.

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  • Lewis C. Cantley 5 shared studies Co-discovered PI3K, the pathway that feeds into mTOR from growth factors
  • Gerta Hoxhaj 4 shared studies Studies how growth signalling through PI3K, AKT and mTOR rewires cell metabolism; as a Manning-lab postdoc she co-authored work on how metformin inhibits mTORC1 in the liver
  • John M. Asara 4 shared studies Mass-spectrometry specialist whose core facility supplied metabolomics and proteomics for several mTOR studies, including measurements of purine, pyrimidine and SAM metabolism downstream of mTORC1.
  • Alexander J. Valvezan 3 shared studies Showed as a Manning-lab postdoc that mTORC1 matches nucleotide production to demand, creating a weak point that can be targeted in tumours with TSC loss. His Rutgers lab found that mTORC1 activity rises and falls through the cell cycle and helps drive entry into mitosis
  • Andrew R. Tee 3 shared studies First author of one of several 2003 papers showing that the TSC1–TSC2 complex acts as a GTPase-activating protein for Rheb
  • David J. Kwiatkowski 3 shared studies Geneticist and physician who studies tuberous sclerosis complex (TSC) and the TSC1/TSC2 genes that restrain mTORC1.
  • Christian C. Dibble 3 shared studies Identified TBC1D7 as the third subunit of the TSC complex that controls mTORC1, as a Manning-lab graduate student. His lab at Beth Israel Deaconess studies how PI3K signalling and nutrient supply are integrated to control mTORC1 and cell metabolism
  • John Blenis 3 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
  • George Talbott 2 shared studies Research assistant in Brendan Manning's mTOR lab at Harvard in 2013 and 2014, who contributed to studies on where the TSC complex sits in the cell and how metformin reaches mTORC1
  • Issam Ben-Sahra 2 shared studies Showed as a postdoc in Brendan Manning's lab that mTORC1 drives both pyrimidine and purine synthesis, through two different mechanisms. His Northwestern lab has extended this to bicarbonate import, SAM synthesis and ERK control of purine production
  • Karen E. Inouye 2 shared studies Metabolic physiologist who runs the Hotamışlıgil lab’s physiology facility, which specialises in glucose clamps, and co-authored two 2026 mouse studies on how feeding controls mTORC1 in liver and muscle.
  • Krystle C. Kalafut 2 shared studies Hepatic mTORC1 and nutrient signalling
  • Leon O Murphy 2 shared studies Cell biologist who led autophagy and mTOR drug discovery at Novartis in Cambridge, Massachusetts, and is now Chief Scientific Officer of Casma Therapeutics, a company that develops drugs acting on the autophagy-lysosome system
  • Madi Y. Cissé 2 shared studies Research associate in the Manning lab and co-author on the two 2026 mouse studies showing which feeding signals switch on mTORC1 in liver and in skeletal muscle.
  • Marc Turner 2 shared studies Research assistant and lab manager in Brendan Manning's mTOR lab at Harvard from 2014 to 2016, who contributed to studies on nucleotide synthesis in tumour cells and on metformin's route to mTORC1
  • Peter M Finan 2 shared studies Biochemist and drug-discovery leader who started the PI 3-kinase drug discovery program at Novartis and ran its Developmental and Molecular Pathways group in Cambridge, Massachusetts, before moving into life-science venture investing
  • Reuben J. Shaw 2 shared studies Showed, in parallel with two other groups, that the tumour suppressor LKB1 directly activates AMPK, and that AMPK brakes mTORC1 by phosphorylating raptor. His Salk lab also linked AMPK to autophagy through ULK1 and helped explain how metformin acts in the liver
  • Samuel C. Lapp 2 shared studies First author of the muscle study showing that feeding-induced mTORC1 activation through AKT–TSC2 drives postprandial protein synthesis but is not needed to build or keep muscle mass.
  • Sue Menon 2 shared studies Showed insulin controls mTORC1 by moving the TSC complex on and off the lysosome
  • Yann Cormerais 2 shared studies Research scientist in the Manning lab who works on how PI3K–AKT–TSC2 signalling controls mTORC1 in living tissues, using mouse models in which TSC2 cannot be phosphorylated by AKT.
  • Diane C. Fingar Studies how mTORC1 and mTORC2 are regulated, especially through site-specific phosphorylation
  • Ernst Hafen Developmental geneticist who used Drosophila to work out how insulin and TOR signalling control cell and body size, including the role of Rheb.
  • Gökhan S. Hotamışlıgil Leads a Harvard laboratory on metabolic disease and was elected to the US National Academy of Sciences in 2026 for achievements in metabolic research
  • James Brugarolas First author of the 2004 study showing that hypoxia switches off mTOR through REDD1 and the TSC1/TSC2 complex; now directs a kidney cancer research program studying signalling and resistance to targeted drugs.
  • Jessica J. Howell Metabolism biologist who, as a postdoc in Brendan Manning's lab at Harvard, worked out how the diabetes drug metformin switches off mTORC1 in the liver, and who later moved into drug and gene-therapy research in industry
  • Katrin Düvel First author of the study showing that mTORC1 switches on a metabolic gene program through HIF1α and SREBP, driving glycolysis, the pentose phosphate pathway and lipid synthesis
  • William G. Kaelin Jr. Cancer researcher who worked out how cells sense oxygen through the VHL and HIF proteins, work recognised by the 2019 Nobel Prize in Physiology or Medicine.

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On the programme

Meetings in the Atlas calendar where Brendan D. Manning is listed among the speakers or organisers.

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