George Thomas
Purified and cloned S6K1, the kinase that became the classic readout of mTORC1 activity. His lab later showed that mice lacking S6K1 resist diet-induced obesity, and that amino acids signal to mTORC1 through the lipid kinase hVps34 (GUL2008)
Principal investigator, Metabolism and Cancer group, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona · previously Scientific Director, Metabolic Disease Institute, University of Cincinnati · Senior Group Leader, Friedrich Miescher Institute, Basel (1979–2004) · PhD, University of California
Metabolism and Cancer group, IDIBELL (L'Hospitalet de Llobregat, Spain) ↗ Lab lineage3 direct trainees → ORCID0000-0003-3518-8149 ↗
Portrait: IDIBELL
George Thomas spent 25 years at the Friedrich Miescher Institute in Basel, where his lab purified and cloned the cell-growth kinases S6K1 and S6K2 — among the first mTORC1 substrates to be identified — and then worked out much of the upstream signalling that controls them, including the TSC1/TSC2 tumour-suppressor complex.
His lab went on to trace S6K1/mTOR signalling into physiology and disease, at the FMI and then, from 2005, at the University of Cincinnati (and since 2012 at IDIBELL in Barcelona): showing that mice lacking S6K1 resist age- and diet-induced obesity while staying insulin-sensitive, that Rheb activation of mTOR/S6K is inhibited by TSC1/2 (one of several groups to report this in 2003), and that the diabetes drug metformin can inhibit mTORC1 independently of AMPK, in a Rag-GTPase-dependent manner.
The timeline below follows Thomas'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 |
|---|---|---|
| 1997 | M | Rapamycin suppresses 5'TOP mRNA translation through inhibition of p70s6k JEF1997 Senior author: rapamycin suppresses translation of 5'TOP mRNAs through p70 S6 kinase (cells; the S6K step was later revised). |
| 1998 | A | Disruption of the p70(s6k)/p85(s6k) gene reveals a small mouse phenotype and a new functional S6 kinase SHI1998 Co-author: S6K1 knockout mice are small, and a second kinase, S6K2, partly takes over S6 phosphorylation. |
| 1999 | A | Drosophila S6 kinase: a regulator of cell size MON1999 Senior author: flies lacking S6 kinase are smaller because their cells are smaller, not fewer. |
| 2000 | A | Hypoinsulinaemia, glucose intolerance and diminished beta-cell size in S6K1-deficient mice PEN2000 Senior author: S6K1-deficient mice have small pancreatic beta cells, low insulin and glucose intolerance. |
| 2000 | M | Genetic and biochemical characterization of dTOR, the Drosophila homolog of the target of rapamycin OLD2000 Co-author: the fly TOR homologue dTOR controls growth through dS6K and points to a parallel amino-acid-sensing branch beside insulin signalling. |
| 2001 | M | Mammalian TOR: a homeostatic ATP sensor DEN2001 Senior author: lowering cellular ATP reduces mTOR signalling independently of amino acids, leading to the proposal that mTOR senses ATP (cells). |
| 2003 | M | Insulin activation of Rheb, a mediator of mTOR/S6K/4E-BP signaling, is inhibited by TSC1 and 2 GAR2003 Shows insulin activation of Rheb, a mediator of mTOR/S6K/4E-BP signalling, is inhibited by the TSC1/TSC2 complex. |
| 2003 | M | Rheb is an essential regulator of S6K in controlling cell growth in Drosophila STO2003 Rheb is an essential regulator of S6K controlling cell growth downstream of TSC in Drosophila. |
| 2004 | A | Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity UMX2004 Shows absence of S6K1 protects mice against age- and diet-induced obesity while enhancing insulin sensitivity. |
| 2006 | A | Hypothalamic mTOR signaling regulates food intake COT2006 Co-author: hypothalamic mTOR signalling acts as a fuel sensor in rats, with brain leucine lowering food intake and rapamycin blunting the effect of leptin on eating. |
| 2008 | M | Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer CAR2008 mTORC1 inhibition activates the MAPK pathway via a PI3K-dependent feedback loop. Seen in tumour biopsies from patients with advanced solid tumours treated with RAD001 (everolimus), where the rise depended on the dosing schedule, and in a mouse prostate cancer model, xenografts and cell lines. |
| 2008 | M | Amino acids activate mTOR complex 1 via Ca2+/CaM signaling to hVps34 GUL2008 Senior author: amino acids raise intracellular calcium, and calcium-calmodulin binding to hVps34 is needed for amino-acid activation of mTORC1 (cells). |
| 2009 | A | Ribosomal protein S6 kinase 1 signaling regulates mammalian life span SEL2009 Deleting S6K1 (a direct mTORC1 effector) extended lifespan in FEMALE mice (+19% median); the effect was not significant in males. It also protected against age-related bone, immune and motor decline. One of the clearest cases of the sex dimorphism catalogued in gap H6 - and a reminder that a single downstream branch, not mTORC1 as a whole, can carry much of the ageing signal. |
| 2010 | M | Metformin, independent of AMPK, inhibits mTORC1 in a rag GTPase-dependent manner KAL2010 Shows metformin inhibits mTORC1 independently of AMPK, in a Rag-GTPase-dependent manner. |
Co-authors in the Atlas 23
People with a profile here who share at least one study with George Thomas.
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- Sara C. Kozma 11 shared studies Studies the S6K/mTOR pathway and how it controls cell growth, ribosome production, diabetes and cancer, including mTOR signalling in liver cancer.
- Ernst Hafen 4 shared studies Developmental geneticist who used Drosophila to work out how insulin and TOR signalling control cell and body size, including the role of Rheb.
- Jacques Montagne 2 shared studies Drosophila geneticist who, working in George Thomas's group, showed that flies lacking S6 kinase are small because their cells are small, not fewer, and helped characterise fly TOR
- Mario Pende 2 shared studies Studies how nutrients and growth factors set cell size and metabolism through mTOR and S6 kinase; as a student in George Thomas's lab he helped show that mice lacking S6K1 have small pancreatic beta-cells and low insulin.
- Takahiro Nobukuni 2 shared studies Showed as first author that amino acids activate mTOR through the lipid kinase hVps34, by a route separate from insulin signalling through TSC, in parallel with a study from Jonathan Backer's laboratory
- Adem Kalender Cell biologist who, in George Thomas's group at the University of Cincinnati, showed that metformin can switch off mTORC1 without AMPK by acting through the Rag GTPases
- Arkaitz Carracedo Cancer biologist who, as first author in 2008, showed that blocking mTORC1 can switch on the MAPK pathway through a PI3K-dependent feedback loop.
- Attila Garami First author of the 2003 study, from George Thomas's group at the Friedrich Miescher Institute, showing that insulin switches on Rheb and that the TSC1-TSC2 complex switches it off
- Benoit Viollet Showed that metformin still lowers liver glucose production without AMPK or LKB1, pointing instead to a drop in cellular energy charge
- Colin Selman Biogerontologist who studies how diet and nutrient-sensing pathways such as insulin/IGF-1 and mTOR set the pace of ageing
- Daniela Cota Studies how the brain senses nutrients and hormones to control food intake and body weight; as a postdoc in Cincinnati she was first author of the rat study that tied hypothalamic mTOR signalling to food intake and leptin action.
- Dominic J. Withers Studies how hormone and nutrient signaling pathways control metabolism and ageing, including the finding that loss of S6K1 extends lifespan in mice.
- Harold Jefferies Biochemist who worked on S6 kinase and 5'TOP mRNA translation in George Thomas's lab and has studied the molecular machinery of autophagy in Sharon Tooze's lab since 2003.
- Hugo Stocker Drosophila geneticist who worked for nearly two decades in Ernst Hafen's group in Zurich and helped show how insulin and TOR signalling set cell and body size in the fruit fly, including the discovery that Rheb is essential for TOR-S6K driven growth
- Johannes L. (Hans) Bos Cancer biologist known for work on Ras mutations and for the small GTPase Rap1 and its activator Epac, a cAMP-regulated switch for cell adhesion
- José Baselga Breast cancer oncologist who led the BOLERO-2 trial showing that the mTOR inhibitor everolimus added to hormone therapy lengthens progression-free survival
- Lewis C. Cantley Co-discovered PI3K, the pathway that feeds into mTOR from growth factors
- Linda Partridge Showed that rapamycin extends fruit-fly lifespan through TORC1, via autophagy and reduced protein synthesis, and that it adds benefit even on top of dietary restriction
- Patrick B. Dennis As a postdoc in George Thomas's lab at the Friedrich Miescher Institute, was first author on the 2001 study proposing that mTOR responds to cellular ATP levels independently of amino acids
- Pawan Gulati First author of the study proposing that amino acids activate mTORC1 through a rise in intracellular calcium and calmodulin binding to hVps34, and later of work linking the obesity gene FTO to amino-acid sensing by mTORC1
- Pier Paolo Pandolfi Showed that ERK directly phosphorylates and inactivates TSC2, wiring Ras/MAPK signalling into mTORC1 control, and that blocking mTORC1 in patients' tumours triggers a feedback rise in MAPK signalling
- Randy J. Seeley Studies how gut and brain signals control appetite, body weight and blood sugar, including why bariatric surgery works; his Cincinnati lab was senior on the rat study linking hypothalamic mTOR to food intake.
- Sung Hee Um Molecular biologist at Sungkyunkwan University School of Medicine whose work centres on the S6 kinases, and first author of the 2004 Nature study showing that mice without S6K1 resist obesity
Every researcher with a profile →
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