Biography
Dr Constantinos Demetriades is a molecular cell biologist working in the field of nutrient sensing and cell growth control. He currently functions as a a Max Planck Research Group Leader (MPRGL) at the Max Planck Institute for Biology of Ageing (MPI-AGE) in Cologne. He is also affiliated to the CECAD Research Center of the University of Cologne, as an Associated PI, and serves as a Faculty Member of the Cologne Graduate School of Ageing Research (CGA). His work has previously elucidated the mechanistic details of mTOR inactivation in response to nutrient starvation, has identified the TSC protein complex as an integral compartment of the amino acid sensing signaling pathway, and has revealed how information from multiple, diverse, cellular stresses is integrated to control cellular physiology.
Dr Demetriades is a European Research Council (ERC) grantee, and has also been awarded a Minerva-Heineman Research grant (funded by the Minna-James-Heineman Foundation), and a Walther Flemming Award from the German Society for Cell Biology (DGZ), recognizing his contribution to the field of cell biology. As an ERC and MPG delegate, Dr Demetriades has also participated as a co-organizer, speaker and expert panel member in the ‘Healthy Ageing’ session of the 2019 World Economic Forum (WEF) meeting in Davos. He is a member of several scientific societies and an Alumnus of the 61st Lindau Nobel Laureate Meeting in Medicine and Physiology.
Education and positions held
- 2019 – present
- Associated PI, CECAD Excellence Cluster, University of Cologne, Germany
- 2017 – present
- Max Planck Research Group Leader, Max Planck Institute for Biology of Ageing (MPI-AGE), Cologne, Germany
- 2010 – 2016
- Postdoctoral Researcher, German Cancer Research Center (DKFZ), Heidelberg, Germany (with Aurelio Teleman)
- 2006 – 2009
- Ph.D. Research Associate, Aristotle University of Thessaloniki, Greece (with George Mosialos)
- 2003 – 2006
- Ph.D. Fellow, Biomedical Sciences Research Center (BSRC) ‘Alexander Fleming’, Athens, Greece (with George Mosialos)
- 1999 – 2003
- Degree (Ptychion) in Biology, Aristotle University of Thessaloniki, Greece
Research Summary
Our work focuses on the intricate molecular and cellular mechanisms of nutrient sensing and growth control, mainly via the regulation of the TSC/mTOR signaling hub. Given the central role 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 ageing and age-related diseases.
We apply high-throughput omics (functional genomic screens, proteomics, metabolomics) to identify novel regulators of key cellular processes; and combine them with state-of-the-art molecular biology, biochemistry, cell biology and high-resolution microscopy techniques to understand the very mechanistic details of their function and to reveal new principles in nutrient sensing and cell growth research. We use cell lines of human, mouse and Drosophila origin, as well as mouse models, to investigate universal and evolutionarily conserved cellular processes, and to understand how cells function in health and what goes wrong in disease and ageing.
The vision of the Demetriades group at the MPI-AGE is to understand:
- How cells sense the presence or the absence of nutrients in their environment to adjust their growth and metabolism accordingly,
- How the dysregulation of these cellular mechanisms contributes to the development of human diseases (cancer, diabetes, neurological disorders) and the ageing process, an
- How we can intervene pharmacologically to target these mTOR-related conditions.
Key publications
- Nüchel J., Tauber M., Nolte JL., Mörgelin M., Türk C., Eckes B., Demetriades C.#, and Plomann M.#, A novel mTORC1-GRASP55 signaling axis reshapes the extracellular proteome upon stress. Mol Cell. 2021 Jul 5;S1097-2765(21)00497-4. doi: 10.1016/j.molcel.2021.06.017.
# Co-corresponding & Co-last authors - 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.#, TSC1 binding to lysosomal PIPs is required for TSC complex translocation and mTORC1 regulation. Mol Cell. 2021 Jul 1;81(13):2705-2721.e8.
- 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., G3BPs tether the TSC complex to lysosomes and suppress mTORC1 signaling. Cell. 2021 Feb 4;184(3):655-674.e27
- Demetriades C.#, Doumpas N., and Teleman AA.#, Regulation of TORC1 in response to amino acid starvation via lysosomal recruitment of TSC2. Cell. 2014 February; 156(4):786-99.
# Co-corresponding authors - 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.
# Co-corresponding authors - Plescher M., Teleman AA.#, and Demetriades C.#, TSC2 mediates hyperosmotic stress-induced inactivation of mTORC1. Scientific Reports. 2015 Sep 8;5:13828.
# Co-corresponding authors - 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.
* Co-first authors - Romero-Pozuelo J., Demetriades C., Schroeder P., and Teleman AA., CycD/Cdk4 and discontinuities in Dpp signaling activate TORC1 in the Drosophila wing disc. Developmental Cell. 2017 Aug 21;42(4):376-387.e5.
# Co-corresponding authors
* Co-first authors