Research Groups

Cell Biology of Nutrient Sensing

The Demetriades lab seeks to uncover new mechanisms and principles of nutrient sensing and metabolic signaling in cells, thus expanding our view on how nutritional cues and stress stimuli influence cellular physiological responses in health, disease, and over ageing.

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  • Info
  • Publications
  • Constantinos Demetriades Visit
    Position

    Associate Professor, Group Leader of the Laboratory for Cell Biology of Nutrient Sensing

    Research fields

    Nutrient sensing, mTOR signaling, metabolism, TSC biology, cancer, ageing, lysosomes, Golgi, unconventional protein secretion

    Postdoctoral Fellows
    Berfu Nur Yigit
    Jamil Nehme
    PhD Students
    Evangelina Krasteva
    Technicians
    Leila Saba

  • Because nutrients are the building blocks for cells to grow and proliferate, nutrient sensing mechanisms ensure that cells only grow when all necessary elements are available and all conditions are optimal. Our work investigates the intricate molecular and cellular mechanisms that govern cell growth, metabolism, and protein recycling in nutrient sufficiency, starvation or stress; and reciprocally connect these processes to secretory pathway activity and the ECM.

    Due to its role as a primary hub in metabolic and nutrient signaling, and a key regulator of virtually all cellular functions, most of our projects center around the master cellular nutrient sensor and growth coordinator, the mTOR kinase; and its main negative upstream regulator, the tumor suppressor TSC complex (Tuberous Sclerosis Complex). Furthermore, given the central function of mTOR in the ageing process—and that dysregulation of the nutrient sensing machinery is a hallmark of ageing—our research investigates fundamental aspects of healthy ageing and age-related diseases.

    To achieve this, we combine high-throughput omics approaches (functional genomic screens, proteomics, metabolomics, interactome/proximome analyses) with state-of-the-art molecular biology, biochemistry, cell biology, gene-editing, and high-resolution microscopy techniques. We make use of established human and mouse cell lines, cancer cell lines, patient-derived cells, as well as model organisms (together with our collaborators), to identify evolutionarily conserved processes and to address multiple fundamental questions. Overall, our vision is to understand: i) how mammalian cells sense the availability of nutrients and the presence of stresses in their environment to adjust their metabolism, growth, and other functions accordingly, ii) how the dysregulation of these cellular mechanisms contributes to the development of human diseases and to the ageing process, and iii) how we can intervene—pharmacologically or nutritionally—to efficiently and specifically target such life-threatening conditions.

    • Nüchel J, Omidi M, Fernandes SA, Tauber M, Pohl S, Plomann M, and Demetriades C. (2026) GRASP55 maintains lysosome function by controlling sorting of lysosomal enzymes at the Golgi. EMBO Reports.
    • Pan J., Teleman A.A., and Demetriades C. (2026) ATM-dependent RHEB phosphorylation couples DNA damage to lysosomal mTORC1 signaling to orchestrate the cellular response to genotoxic stress. bioRxiv.
    • Fernandes S.A., Pan J., Terziyska D.S., Koyuncu S., Ding X., Németh I.B., Wilhelm S., Nüchel J., Al-Gburi S., Gonidas C., Pasparakis M., Mosialos G., Széll M., Teleman A.A., Eming S.A., Vilchez D., and Demetriades C.. (2025) The tumor suppressor CYLD acts as a deubiquitinase for mTOR to constrain its activity. bioRxiv.
    • Kawamura K.*, Diederich AR.*, Gerisch B., Ripa R., Latza C., Steiner J.D., Fernandes SA., Artoni F., Meyer DH., Sant D., Oehm S., Grundmann F., Müller R.-U., Demetriades C., and Antebi A. (2025) Resilience and restoration from fasting-refeeding mediated by a nutrient-regulated linker histone. bioRxiv.
    • Bubb K, Etich J, Probst K, Parashar T, Schuetter M, Dethloff F, Reincke S, Nolte JL, Krüger M, Schlötzer-Schrehard U, Nüchel J, Demetriades C., Giavalisco P, Riemer J, and Brachvogel B (2025) Metabolic rewiring caused by mitochondrial dysfunction promotes mTORC1-dependent skeletal aging. Science Advances.
    • Lamprakis A., and Demetriades C. (2025) TSC1 phosphorylation by lysosomal mTORC1 establishes a minimal autoregulatory feedback loop. bioRxiv.
    • Perri G., French C., Agostinis-Sobrinho C., […], Demetriades C., […], Philippou E., Korolchuk VI., and Shannon OM. (2024) An expert consensus statement on biomarkers of ageing for use in intervention studies. The Journals of Gerontology: Series A.
    • Acharya A., and Demetriades C. (2024) mTORC1 activity licenses its own release from the lysosomal surface. Molecular Cell.
    • Fernandes SA., Angelidaki D-D., Nüchel J., Pan J., Gollwitzer P., Elkis Y., Artoni F., Wilhelm S., Kovacevic-Sarmiento M., and Demetriades C. (2024) Spatial and Functional Separation of mTORC1 Signaling in Response to Different Amino Acid Sources. Nature Cell Biology.
    • Priya A, Antoine-Bally S, Macé AS, Monteiro P, Sabatet V, Remy D, Dingli F, Loew D, Demetriades C. (2023) Gautreau AM, and Chavrier P, Codependencies of mTORC1 signaling and endolysosomal actin structures. Science Advances.
    • Demetriades C. (2023) Malonyl-CoA links lipid metabolism to nutrient signalling by directly inhibiting mTORC1. Nature Cell Biology.
    • Nicastro R, Brohée L, Alba J, Nüchel J, Figlia G, Kipschull S, Gollwitzer P, Romero-Pozuelo J, Fernandes SA, Lamprakis A, Vanni S, Teleman AA, De Virgilio C, and Demetriades C. (2023) Malonyl-CoA is a conserved endogenous ATP-competitive mTORC1 inhibitor. Nature Cell Biology.
    • Suzuki T, Chéret J, Scala FD, Akhundlu A, Gherardini J, Demetrius DL, O'Sullivan JDB, Kuka Epstein G, Bauman AJ, Demetriades C, Paus R. (2023) mTORC1 activity negatively regulates human hair follicle growth and pigmentation. EMBO Rep.
    • Artoni F., Grützmacher N., and Demetriades C., Unbiased Evaluation of Rapamycin’s Specificity as an mTOR Inhibitor. Aging Cell. 2023 May 24;e13888. doi:10.1111/acel.13888
    • Huang W, Kew C, Fernandes SA, Loerhke A, Han L, Demetriades C., and Antebi A. (2022) Decreased spliceosome fidelity and egl-8 intron retention inhibit mTORC1 signaling to promote longevity. Nature Aging.
    • Gollwitzer P, Grützmacher N, Wilhelm S, Kümmel D, and Demetriades C. (2022) A Rag GTPase Dimer Code Defines the Regulation of mTORC1 by Amino Acids. Nature Cell Biology.
    • Demetriades C, Nüchel J, Plomann M. (2021) GRASPing the unconventional secretory machinery to bridge cellular stress signaling to the extracellular proteome. Cell Stress.
    • Fernandes SA, Demetriades C. (2021) The Multifaceted Role of Nutrient Sensing and mTORC1 Signaling in Physiology and Aging. Front Aging.
    • Nüchel J, Tauber M, Nolte JL, Mörgelin M, Türk C, Eckes B, Demetriades C, Plomann M. (2021) An mTORC1-GRASP55 signaling axis controls unconventional secretion to reshape the extracellular proteome upon stress. Mol Cell.
    • Fitzian K, Brückner A, Brohée L, Zech R, Antoni C, Kiontke S, Gasper R, Linard Matos AL, Beel S, Wilhelm S, Gerke V, Ungermann C, Nellist M, Raunser S, Demetriades C, Oeckinghaus A, and Kümmel D, (2021). TSC1 binding to lysosomal PIPs is required for TSC complex translocation and mTORC1 regulation. Molecular Cell.
    • Prentzell MT, Rehbein U, Cadena Sandoval M, De Meulemeester AS, Baumeister R, Brohée L, Berdel B, Bockwoldt M, Carroll B, Chowdhury SR, von Deimling A, Demetriades C, Figlia G; Genomics England Research Consortium; de Araujo MEG, Heberle AM, Heiland I, Holzwarth B, Huber LA, Jaworski J, Kedra M, Kern K, Kopach A, Korolchuk VI, van 't Land-Kuper I, Macias M, Nellist M, Palm W, Pusch S, Ramos Pittol JM, Reil M, Reintjes A, Reuter F, Sampson JR, Scheldeman C, Siekierska A, Stefan E, Teleman AA, Thomas LE, Torres-Quesada O, Trump S, West HD, de Witte P, Woltering S, Yordanov TE, Zmorzynska J, Opitz CA, Thedieck K. (2021) G3BPs tether the TSC complex to lysosomes and suppress mTORC1 signaling. Cell.
    • Romero-Pozuelo J, Demetriades C, Schroeder P, Teleman AA. CycD/Cdk4 and Discontinuities in Dpp Signaling Activate TORC1 in the Drosophila Wing Disc. Dev Cell. 2017 Aug 21;42(4):376-387.e5. doi: 10.1016/j.devcel.2017.07.019. PMID: 28829945.
    • Tsokanos F.*, Albert MA.*, Demetriades C.*, Spirohn K., Boutros M., and Teleman AA., eIF4A inactivates TORC1 in response to amino acid starvation. EMBO J. 2016 Mar 17;35(10):1058-76. doi:10.15252/embj.201593118 Highlighted in: Swierczynska MM., and Hall MN., eIF4A moonlights as an off switch for TORC1. EMBO J. 2016 May 17;35(10):1013-4.
    • Demetriades C.#, Plescher M., and Teleman AA.#, Lysosomal recruitment of TSC2 is a universal response to cellular stress. Nature Communications. 2016 Feb 12;7:10662. doi:10.1038/ncomms10662
    • Plescher M., Teleman AA.#, and Demetriades C.#, TSC2 mediates hyperosmotic stress-induced inactivation of mTORC1. Scientific Reports. 2015 Sep 8;5:13828. doi:10.1038/srep13828
    • Demetriades C., Doumpas N., and Teleman AA., Regulation of TORC1 in response to amino acid starvation via lysosomal recruitment of TSC2. Cell. 2014 February 13; 156(4):786-99. doi:10.1016/j.cell.2014.01.024
    • Antonaki A.*, Demetriades C.*, Polyzos A.*, Banos A.*, Vatsellas G., Lavigne MD., Apostolou E., Mantouvalou E., Papadopoulou D., Mosialos G., and Thanos D., Genomic analysis reveals a novel nuclear factor-κB (NF-κB)-binding site in Alu-repetitive elements. J Biol Chem. 2011 Nov 4;286(44):38768-82.
    • Demetriades C., and Mosialos G., The LMP1 promoter can be transactivated directly by NF-kappaB. J Virology. 2009 May; 83(10):5269-77.
    • Aggelidou E.*, Iordanidou P.*, Demetriades C., Piltsi O., and Hadzopoulou-Cladaras M., Functional characterization of hepatocyte nuclear factor-4 alpha dimerization interface mutants. FEBS J. 2006 May; 273(9):1948-58.
    • Iordanidou P.*, Aggelidou E.*, Demetriades C., and Hadzopoulou-Cladaras M., Distinct amino acid residues may be involved in coactivator and ligand interactions in hepatocyte nuclear factor-4alpha.J Biol Chem. 2005 Jun 10; 280(23):21810-9.
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