Constantinos Demetriades
Showed as a postdoc in Aurelio Teleman's lab that starvation and other stresses pull TSC2 to the lysosome to switch mTORC1 off. His group, at the Max Planck Institute for Biology of Ageing in Cologne from 2017 and at ERIBA in Groningen since 2025, studies how cells sense nutrients and stress through mTORC1 and how this changes with age
Associate Professor, ERIBA, University Medical Center Groningen (since 2025) · Max Planck Research Group Leader, MPI for Biology of Ageing, Cologne (2017–2025) · postdoc, DKFZ Heidelberg (Aurelio Teleman lab, 2010–2016) · PhD, BSRC 'Alexander Fleming' & Aristotle Univ. (George Mosialos lab, 2003–2009) · BSc, Aristotle Univ. of Thessaloniki (2003)
Demetriades Lab, European Research Institute for the Biology of Ageing (ERIBA), UMCG (Groningen, Netherlands) ↗ Lab lineagetrained under Aurelio A. Teleman → ORCID0000-0001-7813-7726 ↗
Portrait: Max Planck Institute for Biology of Ageing
As Teleman-lab postdoc, showed (DEM2014) starvation pulls TSC2 onto the lysosome to directly switch off Rheb/mTORC1 — the missing piece beyond Rag-GTPase relocation. Follow-up (DEM2016): many stress types (energy, hypoxia, osmotic, oxidative, growth-factor withdrawal) independently drive TSC2 to the lysosome — a general damage-control mechanism.
Own MPI-AGE group 2017–2025 (ERC Starting Grant), since 2025 at ERIBA Groningen, continuing to dissect the spatial logic of mTORC1 signaling (2024: mTORC1 does different jobs at different locations). FEBS Young Scientists' Fellowship (2014), Walther Flemming Award (2019).
Milestones in the Atlas
A selection, not a full bibliography: only papers that meet the Atlas inclusion criteria.
| Year | Evidence | Study |
|---|---|---|
| 2014 | M | Regulation of TORC1 in response to amino acid starvation via lysosomal recruitment of TSC2 DEM2014 Amino-acid starvation recruits TSC2 to the lysosome to inactivate Rheb and mTORC1. |
| 2016 | M | Lysosomal recruitment of TSC2 is a universal response to cellular stress DEM2016 Lysosomal TSC2 recruitment is a universal response to many cellular stresses. |
| 2021 | M | G3BPs tether the TSC complex to lysosomes and suppress mTORC1 signaling PRE2021 Adds a physical brake upstream of mTORC1. G3BP1 and G3BP2, known until then as core stress-granule proteins, also sit on the cytoplasmic face of the lysosome and are what holds the TSC complex there; without them TSC cannot reach its target and mTORC1 becomes over-responsive to amino acids and insulin. Loss of G3BP1 reproduces TSC-like hyperactivity phenotypes: faster mTORC1-driven motility in breast cancer cells, with low G3BP1 correlating with worse patient outcome, and disturbed neuronal development in zebrafish. Relevant to the Atlas because it is a lysosomal tethering step that the canonical Rheb/TSC diagram does not show. |
| 2022 | M | A Rag GTPase dimer code defines the regulation of mTORC1 by amino acids GOL2022 The four mammalian Rag GTPase paralogues are not functionally interchangeable: RagC/D determines substrate specificity (RagD favors TFEB/TFE3 phosphorylation via tighter LAMTOR binding), while RagA/B determines the response to amino acid withdrawal (RagB-expressing cells keep mTORC1 lysosomal and active even upon starvation). Author correction issued 2023 (PMID 36536178, no change to conclusions). |
| 2023 | M | Malonyl-CoA is a conserved endogenous ATP-competitive mTORC1 inhibitor NIC2023 Malonyl-CoA, an intermediate of fatty-acid biosynthesis, binds the mTOR catalytic pocket directly and acts as a conserved ATP-competitive inhibitor of mTORC1; when fatty acid synthase is downregulated, rising malonyl-CoA feeds back to dampen mTORC1 activity, linking lipogenic capacity to overall biosynthetic output. |
| 2024 | M | Spatial and functional separation of mTORC1 signalling in response to different amino acid sources FER2024 mTORC1 regulation and downstream substrate phosphorylation are spatially separated: lysosomal mTORC1 (fed by local lysosomal proteolysis) and cytoplasmic mTORC1 (fed by exogenous amino acids) phosphorylate distinct substrates depending on amino acid source, challenging the single lysosomal-hub model. |
| 2025 | PP | The tumor suppressor CYLD acts as a deubiquitinase for mTOR to constrain its activity FER2025 Senior author (preprint): CYLD deubiquitinates mTOR, limiting mTORC1/2 activity; its loss blocks lifespan extension in low-TORC1 worms. |
Co-authors in the Atlas 19
People with a profile here who share at least one study with Constantinos Demetriades.
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- Aurelio A. Teleman 5 shared studies Uses fruit-fly genetics and human cells to study how growth signalling through TOR controls cell and body size. His lab showed that starvation and other stresses move TSC2 to the lysosome to switch mTORC1 off
- Julian Nüchel 3 shared studies Co-author on two Demetriades-lab mTORC1 papers from Cologne: the spatial split of mTORC1 signalling by amino acid source and malonyl-CoA as a direct mTORC1 inhibitor.
- Peter Gollwitzer 3 shared studies First author of the 'Rag dimer code' study showing that the four Rag GTPase paralogues are not interchangeable: RagC/D sets substrate choice and RagA/B sets the response to amino acid withdrawal.
- Sabine Wilhelm 3 shared studies Co-author on two Demetriades-lab studies of amino acid sensing by mTORC1: the Rag GTPase dimer code and the spatial split of mTORC1 signalling.
- Stephanie A. Fernandes 3 shared studies First author of the study showing that lysosomal and cytoplasmic pools of mTORC1 respond to different amino acid sources and phosphorylate different substrates.
- Gianluca Figlia 2 shared studies Cell biologist who studied how mTORC1 senses nutrients in Aurelio Teleman's group at the German Cancer Research Center, including the finding that glutamine is sensed through the kinase GCN2, and who now works at the Institute of Neuropathology in Aachen
- Laura Brohée 2 shared studies Cell biologist who studied how lipid metabolism and the lysosome feed into mTORC1, first at the University of Liège and then at the Max Planck Institute for Biology of Ageing in Cologne
- Alexander M Heberle Cell biologist and Junior Group Leader at the University of Innsbruck who studies how mTOR balances growth signalling and metabolism when cells are under stress, trained in Kathrin Thedieck's systems-biology group
- Bernadette Carroll First author of the study showing why mTORC1 stays switched on in senescent cells, and co-author on G3BP–TSC and senescence-mitophagy work; her own lab studies how nutrient sensing breaks down in ageing cells.
- Claudio De Virgilio Yeast geneticist whose lab found the EGO/Rag GTPase complex that activates TORC1 and showed that the SEACIT complex (Iml1–Npr2–Npr3) switches TORC1 off by acting as a GAP for the Rag GTPase Gtr1.
- Jiyoung Pan PhD student who co-authored the 2024 study showing that mTORC1 does different jobs at the lysosome and away from it, and first author of a 2026 review on why mTORC1 is better seen as a substrate-selective kinase than an on/off switch
- Julian R. Sampson Clinical geneticist who led the consortium that identified the TSC2 gene and led trials of mTOR inhibitors in tuberous sclerosis, including the TRON trial of everolimus for cognition.
- Kathrin Thedieck Senior author of three Atlas studies that treat mTOR signalling as a dynamic network: TSC-independent mTORC2 activation, concurrent AMPK and mTOR activation by amino acids, and G3BP tethering of TSC to lysosomes.
- Lukas A. Huber Cell biologist who studied the p14-MP1 scaffold on late endosomes, a complex later recognised as part of Ragulator (LAMTOR), the lysosomal platform that holds mTORC1 in place
- Mariana de Araujo Cell biologist in Lukas Huber's group in Innsbruck who solved the crystal structure of the Ragulator (LAMTOR) complex, the lysosomal platform on which mTORC1 is switched on
- Mirja Tamara Prentzell First author of the study showing that G3BP proteins anchor the TSC complex to lysosomes, a physical brake on mTORC1; earlier co-author on the dynamic insulin–mTOR network model.
- Raffaele Nicastro Cell biologist at the University of Fribourg who studies TORC1 signalling in yeast and mammals, and first author of the discovery that malonyl-CoA is a natural mTORC1 inhibitor
- Ralf Baumeister Head of the Freiburg department that hosted the Thedieck group during the mTOR network modelling work; co-author on the dynamic mTOR model and the G3BP–TSC study.
- Viktor I. Korolchuk Showed that where lysosomes sit inside the cell tunes mTORC1 activity to nutrient supply. His Newcastle lab found that senescent cells can no longer switch mTORC1 off when nutrients or growth factors are withdrawn, and studies how autophagy and mitophagy decline with age
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