Prof. Dr. Kathrin Thedieck
The Lab for Metabolic Signaling analyses the mTOR pathway and its role in metabolic processes by means of biochemistry, proteomics, and cell biology in human cells and in the genetic model organism C. elegans.
mTOR, the mammalian target of the anti-cancer drug rapamycin, is deregulated in a large number of tumors and is involved in aging related disorders such as metabolic and neurodegenerative diseases. mTOR occurs 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), and energy (ATP), controls growth related processes such as translation, ribosome biogenesis, and autophagy. mTORC2 is also a central metabolic regulator which is involved in lipid and glucose homeostasis.
We analyze the mTOR interactome with proteomic and biochemical methods (Thedieck et al. 2007). Systems biology approaches are adopted to unravel novel regulatory connections within the mTOR network (Dalle Pezze et al. 2012, Sonntag et al. 2012). Recently, we discovered a novel mTORC1 regulator which controls mTORC1 activity and cellular survival under stress (Thedieck et al. 2013). Currently, several research projects are in progress to elucidate novel links between mTOR and its metabolic inputs.
Institut für Biologie und Umweltwissenschaften (IBU) (» Postanschrift)
Department für Neurowissenschaften (» Postanschrift)
(§ designates corresponding author)
Heberle AM, Prentzell MT, van Eunen K, Bakker BM, Grellescheid SN, Thedieck K§ Molecular mechanisms of mTOR regulation by stress.
Molecular and Cellular Oncology, in press. DOI: 10.4161/23723548.2014.970489
Wahane SD, Hellbach N, Prentzell MT, Weise SC, Vezzali R, Kreutz C, Timmer J, Krieglstein K, Thedieck K §, Vogel T§ PI3K-p110-alpha-subtype-signalling mediates survival, proliferation and neurogenesis of cortical progenitor cells via activation of mTORC2.
J. Neurochem. (2014) Jul;130(2):255-67
Arnold CR, Pritz T, Brunner S, Knabb C, Salvenmoser W, Holzwarth B, Thedieck K§, Grubeck-Loebenstein, B§ T cell receptor-mediated activation is a potent inducer of macroautophagy in human CD8+CD28+ T cells but not in CD8+CD28- T cells.
Exp Gerontol. (2014) Jun;54:75-83
Thedieck K§, Holzwarth B, Prentzell MT, Boehlke C, Kläsener K, Ruf S, Sonntag AG, Maerz L, Grellscheid SN, Kremmer E, Nitschke R, Kuehn EW, Jonker JW, Groen AK, Reth M, Hall MN, Baumeister R. Inhibition of mTORC1 by Astrin and Stress Granules Prevents Apoptosis in Cancer Cells.
Cell. (2013) 154, 859-874.
Dalle Pezze P*, Sonntag AG*, Thien A, Prentzell MT, Gödel M, Fischer S, Neumann-Haefelin E, Huber TB, Baumeister R, Shanley DP§, Thedieck K§ A Dynamic Network Model of mTOR Signalling Reveals TSC-Independent mTORC2 Regulation.
SCIENCE Signalling (2012) 27 March Vol 5 Issue 217 ra25 (featured article, mTOR focus issue).
Dalle Pezze P*, Sonntag AG*, Shanley DP§, Thedieck K§ Response to Comment on "A Dynamic Network Model of mTOR Signaling Reveals TSC-Independent mTORC2 Regulation". SCIENCE Signalling (2012) Jul 10;5(232):lc4.
*This is a related yet independent publication in which we respond with new data to several questions regarding the above study, raised by Prof. B. D. Manning, Harvard University, US
Sonntag AG*, Dalle Pezze P*, Shanley DP§, Thedieck K§ A modelling-experimental approach reveals insulin receptor substrate (IRS)-dependent regulation of adenosine monosphosphate-dependent kinase (AMPK) by insulin.
FEBS Journal (2012) Sep;279(18):3314-3328. doi: 10.1111/j.1742-4658.2012.08582.x. Epub 2012 May 3. (Cover story, invited submission to peer-reviewed Systems Biology Special Issue).
Lankisch TO, Metzger J, Negm A, Voßkuhl K, Schiffer E, Siwy J, Weismüller TJ, Schneider AS, Thedieck K, Baumeister R, Zürbig P, Weissinger EM, Manns MP, Mischak H, Wedemeyer J
Bile proteomic profiles differentiates cholangiocarcinoma from primary sclerosing cholangitis and choledocholithiasis.
Hepatology. 2011 Mar;53(3):875-84.
Thedieck K and Hall MN. Translational Control by Amino Acids and Energy.
in The Handbook of Cell Signalling, R. Bradshaw and E. Dennis (editors), 2nd edition, 2009.
Jiang H, Schiffer E, Song Z, Wang J, Zürbig P, Thedieck K, Moes S, Bantel H, Saal N, Jantos J, Brecht M, Jenö P, Hall MN, Hager K, Manns MP, Hecker H, Ganser A, Döhner K, Bartke A, Meissner C, Mischak H, Ju Z, Rudolph KL. Proteins induced by telomere dysfunction and DNA damage represent biomarkers of human aging and disease.
PNAS, 2008, Aug 12;105(32):11299-304.
Thedieck K, Polak P, Kim ML, Molle KD, Cohen A, Jenö P, Arrieumerlou C, Hall MN.
PRAS40 and PRR5-Like Protein Are New mTOR Interactors that Regulate Apoptosis.
PLoS ONE, Nov 2007, 2(11): e1217. doi:10.1371/journal.pone.0001217
Thedieck K, Hain T, Mohamed W, Tindall BJ, Nimtz M, Chakraborty T, Wehland J, Jänsch L. The MprF protein is required for lysinylation of phospholipids in listerial membranes and confers resistance to cationic antimicrobial peptides (CAMPs) on Listeria monocytogenes.
Molecular Microbiology, Dec 2006, Vol 62, p.1325
Thedieck K, Sonntag AG, Dalle Pezze P, Shanley DP.
Method for modeling, optimizing, parameterizing, testing and/or validating a dynamic network or network perturbation. Priority date June 1 2011 (WO2012163440 A8).
Thedieck K, Holzwarth B, Baumeister R
Modulators of the interaction of astrin and raptor, and uses thereof in cancer therapy. Priority date Jan. 11 2013 (WO2014108532 A1).