Reuben J. Shaw
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
Professor, Salk Institute for Biological Studies · postdoc with Lewis Cantley, Harvard Medical School · PhD, MIT (advisor: Tyler Jacks)
Shaw Lab, Salk Institute (La Jolla, California, USA) ↗ Lab lineagetrained under Lewis C. Cantley →
Portrait: Salk Institute for Biological Studies
Reuben Shaw did his postdoctoral work with Lewis Cantley at Harvard, where in 2004 he showed, in parallel with two other groups, that the LKB1 tumour suppressor — mutated in Peutz-Jeghers syndrome and in many lung cancers — directly activates AMPK, the cell's central energy-sensing enzyme. That discovery placed a major cancer gene squarely inside the pathway that senses whether a cell has enough energy to grow.
Since starting his own lab, now at the Salk Institute, Shaw has shown that AMPK directly phosphorylates raptor to shut down mTORC1 when cellular energy is low, a second brake alongside the AMPK-TSC2 route described by Kun-Liang Guan's lab, and that the diabetes drug metformin works partly through this same LKB1–AMPK–mTOR axis. His work ties energy stress, tumour suppression and mTOR signalling into a single, coherent pathway.
The timeline below follows Shaw's contributions gathered in this Atlas.
Milestones in the Atlas
A selection, not a full bibliography: only papers that meet the Atlas inclusion criteria.
| Year | Evidence | Study |
|---|---|---|
| 2004 | M | The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress SHW2004 Shows, in parallel with two other groups, that the LKB1 tumour suppressor directly activates AMPK, linking a major cancer gene to energy-stress signalling. |
| 2004 | M | The LKB1 tumor suppressor negatively regulates mTOR signaling SHAW2004 First author: shows LKB1 is needed to switch off mTOR signalling under low energy through AMPK and TSC2, with raised mTOR signalling in Lkb1 mutant mouse polyps. |
| 2008 | M | AMPK phosphorylation of raptor mediates a metabolic checkpoint GWI2008 Shows AMPK phosphorylates raptor directly, creating a metabolic checkpoint that shuts down mTORC1 under energy stress. |
| 2010 | M | Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy EGA2010 AMPK directly phosphorylates ULK1 to connect energy sensing to autophagy/mitophagy, opposing mTOR. |
| 2017 | M | Metformin Inhibits Hepatic mTORC1 Signaling via Dose-Dependent Mechanisms Involving AMPK and the TSC Complex HOW2017 Co-authors a Manning-lab study showing that metformin inhibits hepatic mTORC1 signalling through dose-dependent mechanisms involving AMPK. |
Co-authors in the Atlas 15
People with a profile here who share at least one study with Reuben J. Shaw.
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- Brendan D. Manning 2 shared studies 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
- Dana M. Gwinn 2 shared studies First author of the 2008 study showing that the energy sensor AMPK switches off mTORC1 by phosphorylating raptor
- Daniel F. Egan 2 shared studies Showed as first author that AMPK directly phosphorylates ULK1, linking low cellular energy to autophagy and mitophagy, and contributed to the finding that AMPK brakes mTORC1 by phosphorylating raptor
- David B. Shackelford 2 shared studies Cancer biologist at UCLA who studies lung tumours that have lost the LKB1 tumour suppressor, the upstream activator of AMPK, and who trained in Reuben Shaw's lab at the Salk Institute
- Lewis C. Cantley 2 shared studies Co-discovered PI3K, the pathway that feeds into mTOR from growth factors
- Maria M. Mihaylova 2 shared studies Studies how intestinal stem cells change with age and how diet shapes their metabolism
- 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.
- Benoit Viollet Showed that metformin still lowers liver glucose production without AMPK or LKB1, pointing instead to a drop in cellular energy charge
- George Talbott 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
- Gerta Hoxhaj 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
- 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
- John M. Asara 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.
- Malene Hansen Showed in worms, alongside a 2007 report from Beth Levine's laboratory, that autophagy is required for dietary restriction to extend lifespan
- Marc Turner 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
- Mondira Kundu Physician-scientist who works out what the autophagy-initiating kinases ULK1 and ULK2 actually do when a cell runs short of fuel
Every researcher with a profile →
On the programme
Meetings in the Atlas calendar where Reuben J. Shaw is listed among the speakers or organisers.
- past Prague Metabolism and Signaling Symposium 2026 ↗ 24–27 Jun 2026 ·
Prague, Czech Republic · ★★★ - past Keystone: Mitochondria Signaling in Physiology and Disease 2026 ↗ 9–12 Feb 2026 ·
Keystone, Colorado, USA · ★
All meetings in the calendar →
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