AG Prof. Dr. Seufferlein
Cancer represents one of the deadliest diseases of our century. Tumor cells are characterized by the ability to grow uncontrollably, change their shape, acquire invasive properties and to spread through the blood stream to other parts of the body where they form metastases. Our lab is committed to investigate various aspects of tumorigenesis and tumor progression of pancreatic cancer (PDAC) and aims at characterizing the role of crucial signaling pathways controlled by several protein kinases.
General interests
Staff
Department Director
Postdocs & Clinician Scientist
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Dr.Hum.Biol. Milena Armacki
Senior PostDoc, Group Leader "In Vivo and Ex Vivo Models"
Schwerpunkte
Mouse models, Ex-vivo models, Microbiota
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Dr. rer. nat Ninel Azoitei
Senior PostDoc, Group Leader "Tumor angiogenesis, Metastasis and Cancer metabolism
Schwerpunkte
Tumour angiogenesis, EMT
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Dr. rer.nat. Tim Eiseler
Senior PostDoc, Group Leader "Exosomes in metastases and inflammation"
Schwerpunkte
Actin Dynamics, Secretion, Exosomes
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Dr.med. Viktoria Hentschel
Clinician Scientist, Fachärztin für Innere Medizin
Schwerpunkte
Organoidbasierte in vitro Modellierung der Darmbarriere
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Ph.D/ M.D students:
Technical assistants
Funding
Join our group
We continuously offers MD positions for performing full-time research.
In case you are interested please send your application documents to
milena.armacki@uniklinik-ulm.de
We continuously offers Master and Bachelor positions.
In case you are interested please send your application documents to
milena.armacki@uniklinik-ulm.de
There are currently no in house funded positions available.
In case you are supported by a fellowship feel free to send your CV and full application documents to group leaders.
Publications of AG Seufferlein
Protein Kinase D1, Reduced in Human Pancreatic Tumors, Increases Secretion of Small Extracellular Vesicles From Cancer Cells That Promote Metastasis to Lung in Mice.
Armacki M@, Polaschek S @, Waldenmaier M , Morawe M, Ruhland C, Schmid R, Lechel A, Tharehalli U , Christoph S, Bektas Y, Li H, Kraus JM, Kestler HA, Kruger S, Ormanns S, Walther P, Eiseler T$ and Seufferlein T1$. Gastroenterology in press 2020. doi: 10.1053/j.gastro.2020.05.052 (@ equal contribution, $ shared senior author).
Sildenafil triggers tumor lethality through altered expression of HSP90 and degradation of PKD2.
Chen L, Liu Y, Becher A, Diepold K, Schmid E, Fehn A, Brunner C, Rouhi A, Chiosis G, Cronauer M, Seufferlein T, Azoitei N.* Carcinogenesis. 2020 pii: bgaa001. doi: 10.1093/carcin/bgaa001
An Immunological Glance on Pancreatic Ductal Adenocarcinoma.
Melzer MK, Arnold F, Stifter K, Zengerling F, Azoitei N, Seufferlein T, Bolenz C, Kleger A. Int J Mol Sci. 2020 May 8;21(9):E3345. doi: 10.3390/ijms21093345.
Adenosine receptor 2B activity promotes autonomous growth, migration as well as vascularization of head and neck squamous cell carcinoma cells.
Wilkat M., Bast H, Drees R, Dünser J, Mahr A, Azoitei N, Marienfeld R, Frank F, Brhel M, Ushmorov A, Greve J, Goldberg-Bockhorn E, Theodoraki MN, Doescher J, Laban S, Schuler PJ, Hoffmann TK, Brunner C. Int J Cancer. 2020 doi: 10.1002/ijc.32835
Concerted regulation of actin polymerization during constitutive secretion by cortactin and PKD2.
Weeber F, Becher A, Seibold T, Seufferlein T, Eiseler T. J Cell Sci. 2019 Dec 13;132(24):jcs232355. doi: 10.1242/jcs.232355. PMID: 31727638.
Physical plasma-triggered ROS induces tumor cell death upon cleavage of HSP90 chaperone.
Bekeschus S, Lippert M, Diepold K, Chiosis G , Seufferlein T, Azoitei N* Scientific Reports 2019 Mar 11;9(1):4112
Variant classification in precision oncology.
Leichsenring J, Horak P, Kreutzfeldt S, Heining C, Christopoulos P, Volckmar AL, Neumann O, Kirchner M, Ploeger C, Budczies J, Heilig CE, Hutter B, Fröhlich M, Uhrig S, Kazdal D, Allgäuer M, Harms A, Rempel E, Lehmann U, Thomas M, Pfarr N, Azoitei N, Bonzheim I, Marienfeld R, Möller P, Werner M, Fend F, Boerries M, von Bubnoff N, Lassmann S, Longerich T, Bitzer M, Seufferlein T, Malek N, Weichert W, Schirmacher P, Penzel R, Endris V, Brors B, Klauschen F, Glimm H, Fröhling S, Stenzinger A. Int J Cancer. 2019 doi: 10.1002/ijc.32358
Midkine Is Elevated After Multiple Trauma and Acts Directly on Human Cardiomyocytes by Altering Their Functionality and Metabolism.
Lackner I, Weber B, Baur M, Haffner-Luntzer M, Eiseler T, Fois G, Gebhard F, Relja B, Marzi I, Pfeifer R, Halvachizadeh S, Lipiski M, Cesarovic N, Pape HC, Kalbitz M; TREAT Research Group. Front Immunol. 2019 Aug 21;10:1920. doi: 10.3389/fimmu.2019.01920. PMID: 31552013; PMCID: PMC6736577.
PKD regulates actin polymerization, neutrophil deformability, and transendothelial migration in response to fMLP and trauma.
Wille C*, Eiseler T*, Langenberger ST, Richter J, Mizuno K, Radermacher P, Knippschild U, Huber-Lang M, Seufferlein T, Paschke S. J Leukoc Biol. 2018 Sep;104(3):615-630. doi: 10.1002/JLB.4A0617-251RR. Epub 2018 Apr 14. PMID: 29656400 (equal contgribution).
Protein kinase D2: a versatile player in cancer biology.
Azoitei N*, Cobbaut M, Becher A, Van Lint J , Seufferlein T. Oncogene 2018, 37(10):1263-1278.
Thirty-eight-negative kinase 1 mediates trauma-induced intestinal injury and multi-organ failure.
Armacki M, Trugenberger AK, Ellwanger AK, Eiseler T, Schwerdt C, Bettac L, Langgartner D, Azoitei N, Halbgebauer R, Groß R, Barth T, Lechel A, Walter BM, Kraus JM, Wiegreffe C, Grimm J, Scheffold A, Schneider MR, Peuker K, Zeißig S, Britsch S, Rose-John S, Vettorazzi S, Wolf E, Tannapfel A, Steinestel K, Reber SO, Walther P, Kestler HA, Radermacher P, Barth TF, Huber-Lang M, Kleger A, Seufferlein T. J Clin Invest. 2018 Nov 1;128(11):5056-5072. doi: 10.1172/JCI97912. Epub 2018 Oct 15. PMID: 30320600; PMCID: PMC6205400.
The armadillo protein p0071 controls KIF3 motor transport.
Becher A*, Eiseler T*, Porzner M, Walther P, Keil R, Bobrovich S, Hatzfeld M, Seufferlein T. J Cell Sci. 2017 Oct 1;130(19):3374-3387. doi: 10.1242/jcs.200170. Epub 2017 Aug 14. PMID: 28808088 (equal contribution).
STK33 participates to HSP90-supported angiogenic program in hypoxic tumors by regulating HIF-1/VEGF signalling pathway.
Liu Y, Steinestel K, Rouhi A, Armacki M, Diepold K, Chiosis G, Simmet T, Seufferlein T, Azoitei N*. Oncotarget 2017, 8(44):77474-77488.
ATM Deficiency Generating Genomic Instability Sensitizes Pancreatic Ductal Adenocarcinoma Cells to Therapy-Induced DNA Damage.
Perkhofer L, Schmitt A, Romero Carrasco MC, Ihle M, Hampp S, Ruess DA, Hessmann E, Russell R, Lechel A, Azoitei N, Lin Q, Liebau S, Hohwieler M, Bohnenberger H, Lesina M, Algül H, Gieldon L, Schröck E, Gaedcke J, Wagner M, Wiesmüller L, Sipos B, Seufferlein T, Reinhardt HC, Frappart PO, Kleger A. Cancer Res. 2017 Oct 15;77(20):5576-5590.
Complement C5a-Induced Changes in Neutrophil Morphology During Inflammation.
Denk S, Taylor RP, Wiegner R, Cook EM, Lindorfer MA, Pfeiffer K, Paschke S, Eiseler T, Weiss M, Barth E, Lambris JD, Kalbitz M, Martin T, Barth H, Messerer DAC, Gebhard F, Huber-Lang MS. Scand J Immunol. 2017 Sep;86(3):143-155. doi: 10.1111/sji.12580. PMID: 28671713; PMCID: PMC5773343.
Src-mediated tyrosine phosphorylation of Protein Kinase D2 at focal adhesions regulates cell adhesion.
Durand N, Bastea LI, Döppler H, Eiseler T, Storz P. Sci Rep. 2017 Aug 25;7(1):9524. doi: 10.1038/s41598-017-10210-7. PMID: 28842658; PMCID: PMC5573332.
PKM2 promotes tumor angiogenesis by regulating HIF-1 through NF-kB activation.
Azoitei N*, Becher A, Steinestel K, Rouhi A, Diepold K, Genze F, Simmet T, Seufferlein T. Molecular Cancer, 2016, Jan 6;15(1):3. doi: 10.1186/s12943-015-0490-2.
Human pluripotent stem cell-derived acinar/ductal organoids generate human pancreas upon orthotopic transplantation and allow disease modelling.
Hohwieler M, Illing A, Hermann PC, Mayer T, Stockmann M, Perkhofer L, Eiseler T, Antony JS, Müller M, Renz S, Kuo CC, Lin Q, Sendler M, Breunig M, Kleiderman SM, Lechel A, Zenker M, Leichsenring M, Rosendahl J, Zenke M, Sainz B Jr, Mayerle J, Costa IG, Seufferlein T, Kormann M, Wagner M, Liebau S, Kleger A. Gut. 2017 Mar;66(3):473-486. doi: 10.1136/gutjnl-2016-312423. Epub 2016 Sep 15. PMID: 27633923; PMCID: PMC5534761.
Tbx3 fosters pancreatic cancer growth by increased angiogenesis and activin/nodal-dependent induction of stemness.
Perkhofer L, Walter K, Costa IG, Carrasco MC, Eiseler T, Hafner S, Genze F, Zenke M, Bergmann W, Illing A, Hohwieler M, Köhntop R, Lin Q, Holzmann KH, Seufferlein T, Wagner M, Liebau S, Hermann PC, Kleger A, Müller M. Stem Cell Res. 2016 Sep;17(2):367-378. doi: 10.1016/j.scr.2016.08.007. Epub 2016 Aug 10. PMID: 27632063.
Protein Kinase D2 Assembles a Multiprotein Complex at the Trans-Golgi Network to Regulate Matrix Metalloproteinase Secretion.
Eiseler T*, Wille C*, Koehler C, Illing A, Seufferlein T. J Biol Chem. 2016 Jan 1;291(1):462-77. doi: 10.1074/jbc.M115.673582. Epub 2015 Oct 27. PMID: 26507660; PMCID: PMC4697185 (equal contribution).
Cortactin is a scaffolding platform for the E-cadherin adhesion complex and is regulated by protein kinase D1 phosphorylation.
Sroka R, Van Lint J, Katz SF, Schneider MR, Kleger A, Paschke S, Seufferlein T, Eiseler T. J Cell Sci. 2016 Jun 15;129(12):2416-29. doi: 10.1242/jcs.184721. Epub 2016 May 13. PMID: 27179075.
A Dynamic Role of TBX3 in the Pluripotency Circuitry.
Russell R, Ilg M, Lin Q, Wu G, Lechel A, Bergmann W, Eiseler T, Linta L, Kumar P P, Klingenstein M, Adachi K, Hohwieler M, Sakk O, Raab S, Moon A, Zenke M, Seufferlein T, Schöler HR, Illing A, Liebau S, Kleger A. Stem Cell Reports. 2015 Dec 8;5(6):1155-1170. doi: 10.1016/j.stemcr.2015.11.003. PMID: 26651606; PMCID: PMC4682344.
Phosphorylation and turnover of paxillin in focal contacts is controlled by force and defines the dynamic state of the adhesion site.
Qin R, Schmid H, Münzberg C, Maass U, Krndija D, Adler G, Seufferlein T, Liedert A, Ignatius A, Oswald F, Eiseler T, von Wichert G. Cytoskeleton (Hoboken). 2015 Feb;72(2):101-12. doi: 10.1002/cm.21209. Epub 2015 Feb 7. PMID: 25620625.
HSP90 supports tumor growth and angiogenesis through PRKD2 protein stabilization
Ninel Azoitei*, Kristina Diepold, Cornelia Brunner, Arefeh Rouhi, Felicitas Genze, Alexander Becher, Hans Kestler, Johan van Lint, Gabriela Chiosis, John Koren III, Stefan Fröhling, Claudia Scholl, Thomas Seufferlein. Cancer Research 2014, 74(23):7125-7136
A two-pronged kinase crucial for the tumor-supporting activity of HSP90.
Ninel Azoitei, Stefan Fröhling, Claudia Scholl, Thomas Seufferlein PRKD2. Molecular and Cellular Oncology 2014, 2:2, e981444;
Protein Kinase D family kinases: roads start to segregate.
Wille C, Seufferlein T, Eiseler T. Bioarchitecture.2014;4(3):111-5. doi: 10.4161/bioa.29273. Epub 2014 May 21. PMID: 24847910; PMCID: PMC4201600.
Protein kinase D2 induces invasion of pancreatic cancer cells by regulating matrix metalloproteinases.
Wille C, Köhler C, Armacki M, Jamali A, Gössele U, Pfizenmaier K, Seufferlein T*, Eiseler T*. Mol Biol Cell. 2014 Feb;25(3):324-36. doi: 10.1091/mbc.E13-06-0334. Epub 2013 Dec 11. PMID: 24336522; PMCID: PMC3907273 .
A novel splice variant of calcium and integrin-binding protein 1 mediates protein kinase D2-stimulated tumour growth by regulating angiogenesis.
Armacki M, Joodi G, Nimmagadda SC, de Kimpe L, Pusapati GV, Vandoninck S, Van Lint J, Illing A, Seufferlein T. Oncogene. 2014. Feb 27;33(9):1167-80. doi: 10.1038/onc.2013.43.
A time frame permissive for Protein Kinase D2 activity to direct angiogenesis in mouse embryonic stem cells.
Müller M, Schröer J, Azoitei N, Eiseler T, Bergmann W, Köhntop R, Lin Q, Costa IG, Zenke M, Genze F, Weidgang C, Seufferlein T, Liebau S, Kleger A. Sci Rep. 2015 Jul 7;5:11742. doi: 10.1038/srep11742. PMID: 26148697; PMCID: PMC4493579.
Protein kinase D1 mediates anchorage-dependent and -independent growth of tumor cells via the zinc finger transcription factor Snail1.
Eiseler T*, Köhler C*, Nimmagadda SC, Jamali A, Funk N, Joodi G, Storz P, Seufferlein T. J Biol Chem. 2012 Sep 21;287(39):32367-80. doi: 10.1074/jbc.M112.370999. Epub 2012 Jul 12. PMID: 22791710; PMCID: PMC3463335
Targeting of KRAS mutant tumors by HSP90 inhibitors involves degradation of STK33.
Ninel Azoitei, Christopher Hoffmann, Jana Ellegast, Claudia Ball, Kerstin Obermayer, Ulrike Gößele, Britta Koch, Katrin Faber, Felicitas Genze, Mark Schrader, Hans Kestler, Hartmut Döhner, Gabriela Chiosis, Hanno Glimm, Stefan Fröhling and Claudia Scholl. Journal of Experimental Medicine (2012), 209: 697-711
Protein kinase D regulates RhoA activity via rhotekin phosphorylation.
Pusapati GV*, Eiseler T*, Rykx A, Vandoninck S, Derua R, Waelkens E, Van Lint J, von Wichert G, Seufferlein T. J Biol Chem. 2012 Mar 16;287(12):9473-83. doi: 10.1074/jbc.M112.339564. Epub 2012 Jan 6. PMID: 22228765; PMCID: PMC3308793. (equal contribution)
Neuregulin mediates F-actin-driven cell migration through inhibition of protein kinase D1 via Rac1 protein.
Döppler H, Bastea LI, Eiseler T, Storz P. J Biol Chem. 2013 Jan 4;288(1):455-65. doi: 10.1074/jbc.M112.397448. Epub 2012 Nov 12. PMID: 23148218; PMCID: PMC3537043.
Keratin 8 phosphorylation regulates keratin reorganization and migration of epithelial tumor cells.
Armacki M, Busch T, Eiseler T, Joodi G, Temme C, Jansen J, von Wichert G, Omary MB, Spatz J, Seufferlein T. J Cell Sci. 2012 May 1;125(Pt 9):2148-59. doi: 10.1242/jcs.080127. Epub 2012 Feb 17. PMID: 22344252; PMCID: PMC3367938.
Protein kinase D2 is a novel regulator of glioblastoma growth and tumor formation
Ninel Azoitei, Alexander Kleger, Nina Schoo, Dietmar Rudolf Thal, Cornelia Brunner, Ganesh Varma Pusapati, Alina Filatova, Felicitas Genze, Peter Möller, Til Acker, Rainer Kuefer, Johan Van Lint, Heinrich Baust, Guido Adler, Thomas Seufferlein. Neuro-Oncology (2011), 13(7): 710-724
Protein kinase D2 is a crucial regulator of tumor cell-endothelial cell communication in gastrointestinal tumors.
Ninel Azoitei, Ganesh Varma Pusapati, Alexander Kleger, Peter Möller, Rainer Küfer, Felicitas Genze, Martin Wagner, Johan van Lint, Peter Carmeliet, Guido Adler, Thomas Seufferlein. Gut (2010), 59(10): 1316-30.
Protein kinase D controls actin polymerization and cell motility through phosphorylation of cortactin.
Eiseler T, Hausser A, De Kimpe L, Van Lint J, Pfizenmaier K. J Biol Chem. 2010 Jun 11;285(24):18672-83. doi: 10.1074/jbc.M109.093880. Epub 2010 Apr 2. PMID: 20363754; PMCID: PMC2881792.
A novel protein kinase D phosphorylation site in the tumor suppressor Rab interactor 1 is critical for coordination of cell migration.
Ziegler S, Eiseler T, Scholz RP, Beck A, Link G, Hausser A. Mol Biol Cell. 2011 Mar 1;22(5):570-80. doi: 10.1091/mbc.E10-05-0427. Epub 2011 Jan 5. PMID: 21209314; PMCID: PMC3046055.
Protein Kinase D2 Is an Essential Regulator of Murine Myoblast Differentiation.
Alexander Kleger, Christiane Loebnitz., Ganesh V. Pusapati, Milena Armacki, MartinMuller, Stefan Tumpel, Anett Illing, Daniel Hartmann, Cornelia Brunner, StefanLiebau, Karl L. Rudolph, Guido Adler1, Thomas Seufferlein. PLOS One 2011
Role of the Second Cysteine-Rich Domain and Pro275 in Protein Kinase D2 Interaction with ADP-Rybosylation Factor 1, Trans-Golgi Network Recruitment, and Protein Transport
Ganesh Varma Pusapati,* Denis Krndija,* Milena Armacki,† Gotz von Wichert,*
Julia von Blume,‡ Vivek Malhotra,‡ Guido Adler,* and Thomas Seufferlein. Molecular Biology of the Cell.2010
Characterization of cortactin as an in vivo protein kinase D substrate: Interdependence of sites and potentiation of Src.
L. de Kimpe, K. Janssens, R. Derua, M.Armacki, S. Goicoechea, C. Otey, E. Waelkens, S. Vandoninck, J.R. Vandenheede, T. Seufferlein, J.van Lint. Cellular Signalling 2009
Loss of cell-cell contacts induces NF-kappaB via RhoA-mediated activation of protein kinase D1.
Cowell CF, Yan IK, Eiseler T, Leightner AC, Döppler H, Storz P. J Cell Biochem. 2009 Mar 1;106(4):714-28. doi: 10.1002/jcb.22067. PMID: 19173301; PMCID: PMC4556359.
Protein kinase D1 regulates cofilin-mediated F-actin reorganization and cell motility through slingshot.
Eiseler T, Döppler H, Yan IK, Kitatani K, Mizuno K, Storz P. Nat Cell Biol. 2009 May;11(5):545-56. doi: 10.1038/ncb1861. Epub 2009 Mar 29. PMID: 19329994; PMCID: PMC2761768.
Protein kinase D1 regulates matrix metalloproteinase expression and inhibits breast cancer cell invasion.
Eiseler T, Döppler H, Yan IK, Goodison S, Storz P. Breast Cancer Res. 2009;11(1):R13. doi: 10.1186/bcr2232. Epub 2009 Feb 25. PMID: 19243594; PMCID: PMC2687718.
Thirty-eight-negative kinase 1 (TNK1) facilitates TNF-induced apoptosis by blocking NF-kB activation
Ninel Azoitei, Andreas Brey, Tobias Bush, Simone Fulda, Guido Adler, Thomas Seufferlein. Oncogene (2007), 26(45): 6536-6545
PKD is recruited to sites of actin remodelling at the leading edge and negatively regulates cell migration.
Eiseler T, Schmid MA, Topbas F, Pfizenmaier K, Hausser A. FEBS Lett. 2007 Sep 4;581(22):4279-87. doi: 10.1016/j.febslet.2007.07.079. Epub 2007 Aug 10. PMID: 17707375.
Activation of I kappa B kinase complex is sufficient for neuronal differentiation of PC12 cells
Ninel Azoitei, Thomas Wirth, Bernd Baumann. Journal of Neurochemistry, (2005), 93(6):1487-1501
NF-kB is essential for epithelial-mesenchymal transition and metastasis in a model of breast cancer progression
Margit Huber, Ninel Azoitei, Bernd Baumann, Stefan Grünert, Andreas Sommer, Hubert Pehamberger, Norbert Kraut, Hartmut Beug and Thomas Wirth Journal of Clinical Investigation, (2004), 114: 569-581
Protein kinase C (PKC)eta- mediated PKC mu activation modulates ERK and JNK signal pathways.
Brändlin I, Hübner S, Eiseler T, Martinez-Moya M, Horschinek A, Hausser A, Link G, Rupp S, Storz P, Pfizenmaier K, Johannes FJ. J Biol Chem. 2002 Feb 22;277(8):6490-6. doi: 10.1074/jbc.M106083200. Epub 2001 Dec 6. PMID: 11741879.
Protein kinase C(mu) regulation of the JNK pathway is triggered via phosphoinositide-dependent kinase 1 and protein kinase C(epsilon).
Brändlin I, Eiseler T, Salowsky R, Johannes FJ. J Biol Chem. 2002 Nov 22;277(47):45451-7. doi: 10.1074/jbc.M205299200. Epub 2002 Sep 9. PMID: 12223477.