prof. dr. K. (Kathrin) Thedieck

Associate Professor

Research

Research interests

Prof. Dr. Kathrin Thedieck joined  the University Medical Center Groningen (UMCG) and Oldenburg University  in 2013 in the frame of the European Medical School (EMS).

 

The Lab for Metabolic Signaling studies the control of metabolic homeostasis by kinase networks centred on the mammalian target of rapamycin (mTOR). We adopt cell biology, biochemistry, proteomics, and systems approaches.

mTOR is a central controller of metabolism and ageing. mTOR is dysregulated in most cancers as well as in metabolic and neurodegenerative and congenital disorders, and is therefore of major biomedical interest as a drug target and biomarker. The kinase mTOR is at the center of a large signaling network and exists in two structurally and functionally distinct multiprotein complexes, named mTOR complex 1 (mTORC1) and mTORC2. mTORC1, in response to growth factors (insulin), nutrients (amino acids), energy (ATP), and stress (e.g., reactive oxygen species) controls growth related processes such as translation, ribosome biogenesis, and autophagy. mTORC2 is a central metabolic regulator as well which is involved in lipid and glucose homeostasis.

mTOR, via a complex kinase network, regulates virtually all anabolic processes at the cellular and organismal level. But how are specific metabolic responses to distinct metabolic inputs achieved? We hypothesize that different molecular networks transduce specific metabolic stimuli and mTOR-dependent metabolic responses. Hence, we aim to identify novel mTOR network components and delineate their interconnection in relation to different metabolic inputs and outputs. To this end, our lab analyzes the mTOR interactome and phosphotargets using proteomic and biochemical methods (Schwarz et al. 2015). To deal with mTOR network complexity, systems biology approaches are adopted to unravel novel regulatory connections governing mTOR’s activity and outputs (Dalle Pezze 2016; Sonntag et al 2012; Dalle Pezze 2012). We functionally characterize novel mTOR regulators by cell biological approaches. For example, we investigate regulators which control mTOR activity and cellular survival under stress (Heberle et al. 2015; Thedieck et al. 2013), and we unravel mTOR crosstalk with other signaling networks such as TGFbeta (Thien et al. 2015) and autophagy (Ruf et al. 2017).

Read further on the website of the Lab for Metabolic Signaling.

 

 

Publications
  1. The PI3K and MAPK/p38 pathways control stress granule assembly in a hierarchical manner

    Heberle, A. M., Razquin Navas, P., Langelaar-Makkinje, M., Kasack, K., Sadik, A., Faessler, E., Hahn, U., Marx-Stoelting, P., Opitz, C. A., Sers, C., Heiland, I., Schäuble, S. & Thedieck, K., Apr-2019, In : Life science alliance. 2, 2, 22 p.

    Research output: Contribution to journalArticleAcademicpeer-review

  2. Tomatidine, a novel antiviral compound towards dengue virus

    Diosa-Toro, M., Troost, B., van de Pol, D., Heberle, A. M., Urcuqui-Inchima, S., Thedieck, K. & Smit, J. M., Jan-2019, In : Antiviral Research. 161, p. 90-99 10 p.

    Research output: Contribution to journalArticleAcademicpeer-review

  3. Partially non-homogeneous dynamic Bayesian networks based on Bayesian regression models with partitioned design matrices

    Shafiee Kamalabad, M., Heberle, A. M., Thedieck, K. & Grzegorczyk, M., 5-Nov-2018, In : Bioinformatics (Oxford, England). 10 p.

    Research output: Contribution to journalArticleAcademicpeer-review

  4. Upregulation of tryptophanyl-tRNA synthethase adapts human cancer cells to nutritional stress caused by tryptophan degradation

    Adam, I., Dewi, D. L., Mooiweer, J., Sadik, A., Mohapatra, S. R., Berdel, B., Keil, M., Sonner, J. K., Thedieck, K., Rose, A. J., Platten, M., Heiland, I., Trump, S. & Opitz, C. A., 2018, In : OncoImmunology. 7, 12, 14 p., 1486353.

    Research output: Contribution to journalArticleAcademicpeer-review

  5. PLK1 (polo like kinase 1) inhibits MTOR complex 1 and promotes autophagy

    Ruf, S., Heberle, A. M., Langelaar-Makkinje, M., Gelino, S., Wilkinson, D., Gerbeth, C., Schwarz, J. J., Holzwarth, B., Warscheid, B., Meisinger, C., van Vugt, M. A. T. M., Baumeister, R., Hansen, M. & Thedieck, K., 2017, In : Autophagy. 13, 3, p. 486-505 20 p.

    Research output: Contribution to journalArticleAcademicpeer-review

  6. A systems study reveals concurrent activation of AMPK and mTOR by amino acids

    Pezze, P. D., Ruf, S., Sonntag, A. G., Langelaar-Makkinje, M., Hall, P., Heberle, A. M., Navas, P. R., van Eunen, K., Tölle, R. C., Schwarz, J. J., Wiese, H., Warscheid, B., Deitersen, J., Stork, B., Fäßler, E., Schäuble, S., Hahn, U., Horvatovich, P., Shanley, D. P. & Thedieck, K., 21-Nov-2016, In : Nature Communications. 7, p. 1-19 19 p., 13254.

    Research output: Contribution to journalArticleAcademicpeer-review

  7. Functional Proteomics Identifies Acinus L as a Direct Insulin- and Amino Acid-Dependent Mammalian Target of Rapamycin Complex 1 (mTORC1) Substrate

    Schwarz, J. J., Wiese, H., Toelle, R. C., Zarei, M., Dengjel, J., Warscheid, B. & Thedieck, K., Aug-2015, In : Molecular & Cellular Proteomics. 14, 8, p. 2042-2055 14 p.

    Research output: Contribution to journalArticleAcademicpeer-review

  8. Tumor-intrinsic PD-L1 signals regulate cell growth, pathogenesis and autophagy in ovarian cancer and melanoma

    Clark, C. A., Gupta, H. B., Sareddy, G., Pandeswara, S., Lao, S., Yuan, B., Drerup, J. M., Padron, A., Conejo-Garcia, J., Murthy, K., Liu, Y., Turk, M. J., Thedieck, K., Hurez, V., Li, R., Vadlamudi, R. & Curiel, T. J., 1-Dec-2016, In : Cancer Research. 76, 23, p. 6964-6974 11 p.

    Research output: Contribution to journalArticleAcademicpeer-review

  9. TSC1 Activates TGF-beta-Smad2/3 Signaling in Growth Arrest and Epithelial-to-Mesenchymal Transition

    Thien, A., Prentzell, M. T., Holzwarth, B., Klaesener, K., Kuper, I., Boehlke, C., Sonntag, A. G., Ruf, S., Maerz, L., Nitschke, R., Grellscheid, S-N., Reth, M., Walz, G., Baumeister, R., Neumann-Haefelin, E. & Thedieck, K., 9-Mar-2015, In : Developmental Cell. 32, 5, p. 617-630 14 p.

    Research output: Contribution to journalArticleAcademicpeer-review

  10. Molecular mechanisms of mTOR regulation by stress

    Heberle, A. M., Prentzell, M. T., Van Eunen, K., Bakker, B. M., Grellscheid, S. N. & Thedieck, K., 3-Apr-2015, In : Molecular & Cellular Oncology. 2, 2, 16 p., e970489.

    Research output: Contribution to journalArticleAcademicpeer-review

  11. Inhibition of mTORC1 by Astrin and Stress Granules Prevents Apoptosis in Cancer Cells

    Thedieck, K., Holzwarth, B., Prentzell, M. T., Boehlke, C., Klaesener, K., Ruf, S., Sonntag, A. G., Maerz, L., Grellscheid, S-N., Kremmer, E., Nitschke, R., Kuehn, E. W., Jonker, J. W., Groen, A. K., Reth, M., Hall, M. N. & Baumeister, R., 15-Aug-2013, In : Cell. 154, 4, p. 859-874 16 p.

    Research output: Contribution to journalArticleAcademicpeer-review

  12. A dynamic network model of mTOR signaling reveals TSC-independent mTORC2 regulation

    Dalle Pezze, P., Sonntag, A. G., Thien, A., Prentzell, M. T., Gödel, M., Fischer, S., Neumann-Haefelin, E., Huber, T. B., Baumeister, R., Shanley, D. P. & Thedieck, K., 27-Mar-2012, In : Science signaling. 5, 217, p. ra25

    Research output: Contribution to journalArticleAcademicpeer-review

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