Geley Stephan, ao.Univ.-Prof. Dr.med.univ.

University / Clinic: Innsbruck Medical University
Institute: Biocenter, Division of Pathophysiology
 
Research Area: Cell Biology, Cancer Research

Email: stephan.geley@i-med.ac.at
Web: www.tkfi.at/dmp/


Research Topic:
The anaphase promoting complex (APC/C), a large multisubunit ubiquitin ligase, is required for the degradation of mitotic cyclins, which starts during prometaphase and terminates in late G1-phase. By expressing non-degradable cyclin B1, we have shown that cells arrest at various late mitotic stages in a dose-dependent manner, suggesting that late mitotic events might exhibit differential sensitivity towards cyclin dependent kinase (CDK) activity. In order to understand how exit from mitosis is coordinated, we are looking for CDK substrates, such as the chromokinesin hKid or the RhoA GEF Ect2, that are involved in the regulation of anaphase and cytokinesis, respectively. We will extend our search for mitotic phosphoproteins by using the phosphopeptide binding domains of the mitosis regulators Plk1 and Pin1 as affinity reagents for phosphorlyated peptides that will be analyzed by LC-MS. During early mitosis, the APC/C is activated by Cdc20 until it is exchanged for by Fzr1, a related WD40 repeat protein, shortly after the beginning of anaphase. While Cdc20 is essential for the onset of anaphase and cyclin degradation, the function of Fzr1 is less well understood and we have therefore generated a mouse strain carrying a conditional Fzr1 allele. Analysis of Fzr1 deficient cells and tissues will allow us, for the first time, to examine the role of the APC/C in G1-phase during development and tissue homeostasis and will test its possible role as a tumor suppressor gene. халаты женские
халаты киев


Project:
  Analysis of FZR1 function in tissue homeostasis
details ...

Selected publications:
 
  Fava L, Schuler F, Sladky V, Haschka M, Soratroi C, Eiterer L, Demetz E, Weiss G, Geley S, Nigg E, Villunger A
The PIDDosome activates p53 in response to supernumerary centrosomes
Genes Dev. 2017 Jan 1;31(1):34-45. doi: 10.1101/gad.289728.116.

  Schuler F, Weiss JG, Lindner SE, Lohmüller M, Herzog S, Spiegl SF, Menke P, Geley S, Labi V, Villunger A
Checkpoint kinase 1 is essential for normal B cell development and lymphomagenesis
Nat Commun. 2017 Nov 22;8(1):1697. doi: 10.1038/s41467-017-01850-4. PubMed PMID: 29167438; PubMed Ce

  Pfeiffenberger E, Sigl R, Geley S
Conditional RNAi Using the Lentiviral GLTR System.
Methods Mol Biol. 2016;1448:121-38. doi: 10.1007/978-1-4939-3753-0_10.

  Haschka M, Soratroi C, Kirschnek S, Häcker G, Hilbe R, Geley S, Villunger A, Fava L
The NOXA-MCL1-BIM axis defines lifespan on extended mitotic arrest.
Nat Commun. 2015 Apr 29;6:6891.

  Vosper J, Masuccio A, Kullmann M, Ploner C, Geley S, Hengst L
Statin-induced depletion of geranylgeranyl pyrophosphate inhibits cell proliferation by a novel pathway of Skp2 degradation
Oncotarget. 2015 Feb 20;6(5):2889-902

  Fava L, Rainer J, Haschka M, Geley S, Villunger A
Beclin 1 is dispensable for chromosome congression and proper outer kinetochore assembly.
EMBO Rep. 2015 Oct;16(10):1233-6. doi: 10.15252/embr.201540731. Epub 2015 Aug 20.

  Ofer P, Heidegger I, Eder I, Schöpf B, Neuwirt H, Geley S, Klocker H, Massoner P
Both IGF1R and INSR Knockdown Exert Antitumorigenic Effects in Prostate Cancer In Vitro and In Vivo.
Mol Endocrinol. 2015 Dec;29(12):1694-707. doi: 10.1210/me.2015-1073. Epub 2015 Oct 9.

  Höfer J, Kern J, Ofer P, Eder I, Schäfer G, Dietrich D, Kristiansen G, Geley S, Rainer J, Gunsilius E, Klocker H, Culig Z, Puhr M
SOCS2 correlates with malignancy and exerts growth-promoting effects in prostate cancer.
Endocr Relat Cancer. 2014 Jan 30;

  Etemad Ahari S, Obermair G, Bindreither D, Benedetti A, Stanika R, Di Biase V, Burtscher V, Koschak A, Kofler R, Geley S, Wille A, Lusser A, Flockerzi V, Flucher B
Differential neuronal targeting of a new and two known calcium channel β4 subunit splice variants correlates with their regulation of gene expression.
J Neurosci. 2014 Jan 22;34(4):1446-61

  Puhr M, Höfer J, Neuwirt H, Eder I, Kern J, Schäfer G, Geley S, Heidegger I, Klocker H, Culig Z
PIAS1 is a crucial factor for prostate cancer cell survival and a valid target in docetaxel resistant cells.
Oncotarget. 2014 Dec 15;5(23):12043-56.

  Manzl C, Fava L, Krumschnabel G, Peintner L, Tanzer M, Soratroi C, Bock F, Schuler F, Luef B, Geley S, Villunger A
Death of p53-defective cells triggered by forced mitotic entry in the presence of DNA damage is not uniquely dependent on Caspase-2 or the PIDDosome.
Cell Death Dis. 2013 Dec 5;4:e942.

  Thöni C, Vogel G, Tancevski I, Geley S, Lechner S, Pfaller K, Hess MW, Müller T, Janecke A, Avitzur Y, Muise A, Cutz E, Huber L
Microvillus inclusion disease: loss of Myosin vb disrupts intracellular traffic and cell polarity.
Traffic. 2014 Jan;15(1):22-42.

  Ottina E, Grespi F, Tischner D, Soratroi C, Geley S, Ploner A, Reichardt H, Villunger A, Herold M
Targeting anti-apoptotic A1/Bfl-1 by in vivo RNAi reveals multiple roles in leukocyte development in mice.
Blood. 2012 Jun 21;119(25):6032-42.

  Rainer J, Lelong J, Bindreither D, Mantinger C, Ploner C, Geley S, Kofler R
Research resource: transcriptional response to glucocorticoids in childhood acute lymphoblastic leukemia.
Mol Endocrinol. 2012 Jan;26(1):178-93.

  Barisic M, Geley S
Spindly switch controls anaphase: spindly and RZZ functions in chromosome attachment and mitotic checkpoint control.
Cell Cycle. 2011 Feb 1;10(3):449-56. Epub 2011 Feb 1

  Grespi F , Ottina E, Yannoutsos N, Geley S, Villunger A
Generation and evaluation of an IPTG-regulated version of Vav-gene promoter for mouse transgenesis.
PLoS ONE 6(3): e18051. doi:10.1371/journal.pone.0018051

  Barisic M, Sohm B, Mikolcevic P, Wandke C, Rauch V, Ringer T, Hess M, Bonn G, Geley S
Spindly/CCDC99 is required for efficient chromosome congression and mitotic checkpoint regulation
Mol Biol Cell. 2010 Jun 15;21(12):1968-81. Epub 2010 Apr 28

  Grespi F, Soratroi C, Krumschnabel G, Sohm B, Ploner C, Geley S, Hengst L, Häcker G, Villunger A
BH3-only protein Bmf mediates apoptosis upon inhibition of CAP-dependent protein synthesis
Cell Death Differ. 2010 Nov;17(11):1672-83

  Mansha M, Carlet M, Ploner C, Gruber G, Wasim M, Wiegers G, Rainer J, Geley S, Kofler R
Functional analyses of Src-like adaptor (SLA), a glucocorticoid-regulated gene in acute lymphoblastic leukemia.
Leuk Res. 2010 Apr;34(4):529-34. Epub 2009 Jul 29.

  Frenzel A, Labi V, Chmelewskij W, Ploner C, Geley S, Fiegl H, Tzankov A, Villunger A.
Suppression of B-cell lymphomagenesis by the BH3-only proteins Bmf and Bad
Blood. 2010 Feb 4;115(5):995-1005.

  Ploner C, Rainer J, Lobenwein S, Geley S, Kofler R
Repression of the BH3-only molecule PMAIP1/Noxa impairs glucocorticoid sensitivity of acute lymphoblastic leukemia cells.
Apoptosis. 2009 Jun;14(6):821-8.

  Subramanyam P, Obermair G, Baumgartner S, Gebhart M, Striessnig J, Kaufmann W, Geley S, Flucher B
Activity and calcium regulate nuclear targeting of the calcium channel beta4b subunit in nerve and muscle cells
Channels 5:343-55.

  Ploner C, Rainer J, Lobenwein, Geley S, Kofler R
Repression of the BH3-only molecule PMAIP1/Noxa impairs glucocorticoid sensitivity of acute lymphoblastic leukemia cells.
Apoptosis 14:821-828.

  Sigl R, Wandke C, Rauch V, Kirk J, Hunt T, Geley S. (2009)
Loss of the mammalian APC/C activator FZR1 shortens G1 and lengthens S phase but has little effect on exit from mitosis
J Cell Sci. 2009 Nov 15;122(Pt 22):4208-17

  Massoner P, Colleselli D, Matscheski A, Pircher H, Geley S, Jansen-Dürr P, Klocker H
Novel mechanism of IGF-binding protein-3 action on prostate cancer cells: inhibition of proliferation, adhesion, and motility
Endocr Relat Cancer. 16:795-808

  Ploner C, Rainer J, Lobenwein S, Geley S, Kofler R
Repression of the BH3-only molecule PMAIP1/Noxa impairs glucocorticoid sensitivity of acute lymphoblastic leukemia cells.
Apoptosis. 2009 Jun;14(6):821-8.

  Geley S, Hengst L
Zellzyklus. In: Die Onkologie.
2. Auflage. W. Hiddemann, Bartram C. R. (Eds.). Springer Verlag.

  Haffner M, Jurgeit A, Berlato C, Geley S, Parajuli N, Yoshimura A, Doppler W
Interaction and functional interference of glucocorticoid receptor and SOCS1.
J Biol Chem, 283(32):22089-22096

  Ploner C, Rainer J, Niederegger H, Eduardoff M, Villunger A, Geley S, Kofler R.
The BCL2 rheostat in glucocorticoid-induced apoptosis of acute lymphoblastic leukemia.
Leukemia. 2008 Feb;22(2):370-7. Epub 2007 Nov 29.

  Ploner C, Rainer J, Niederegger H, Eduardoff M, Villunger A, Geley S, Kofler R
The BCL2 rheostat in glucocorticoid-induced apoptosis of acute lymphoblastic leukemia.
Leukemia 22:370-377.

  Ploner C, Rainer J, Niederegger H, Eduardoff M, Villunger A, Geley S, Kofler R
The BCL2 rheostat in glucocorticoid-induced apoptosis of acute lymphoblastic leukemia.
Leukemia. 2008 Feb;22(2): 370-7.

  Jurgeit A, Berlato C, Obrist P, Ploner C, Massoner P, Schmölzer J, Haffner M, Klocker H, Huber L, Geley S, Doppler W
Insulin-Like Growth Factor Binding Protein (Igfbp)-5 Enters Vesicular Structures but Not the Nucleus.
Traffic 8(12):1815-1828

  Teis D, Kurzbauer R, Hilber D, Erlacher M, Villunger A, Geley S, Bohn G, Klein C, Hess M, Huber L
The p14/MP1-scaffold complex is required for endosomal ERK activation and cell cycle progression in vivo.
J Cell Biol. 2006 Dec 18;175(6):861-8.

  Schmidt S, Rainer J, Riml S, Ploner C, Jesacher S, Achmüller C, Presul E, Skvortsov S, Crazzolara R, Fiegl M, Raivio T, Jänne O, Geley S, Meister B, Kofler R
Identification of glucocorticoid response genes in children with acute lymphoblastic leukemia.
Blood. 2006; Mar 1; 107(5): 2061-9

  Teis D, Taub N, Kurzbauer R, Hilber D, de Araujo M, Erlacher M, Offterdinger M, Villunger A, Geley S, Bohn G, Klein C, Hess M, Huber L
p14-MP1-MEK1 signaling regulates endosomal traffic and cellular proliferation during tissue homeostasis.
J Cell Biol. 2006 Dec 18;175(6):861-

  Wolf F, Geley S
A simple and stable autofocusing protocol for long multidimensional live cell microscopy.
J Microsc., 221(Pt 1):72-7.

  Wandke C, Geley S
Generation and characterization of an hKid-specific monoclonal antibody.
Hybridoma (Larchmt). 2006 Feb;25(1):41-3

  Schmidt S, Rainer J, Riml S, Ploner C, Jesacher S, Achmüller C, Presul E, Skvortsov S, Crazzolara R, Fiegl M, Raivio T, Jänne O, Geley S, Meister B, Kofler R
Identification of glucocorticoid-response genes in children with acute lymphoblastic leukemia.
Blood. 2006 Mar 1;107(5):2061-9. Epub 2005 Nov 17.

  Schmidt S, Rainer J, Riml S, Ploner C, Jesacher S, Achmüller C, Presul E, Skvortsov S, Crazzolara R, Fiegl M, Raivio T, Jänne O, Geley S, Meister B, Kofler R
Identification of glucocorticoid response genes in children with acute lymphoblastic leukemia.
Blood 107:2061-2069.

  Schmidt S, Rainer J, Riml S, Ploner C, Jesacher S, Achmüller C, Presul E, Skvortsov S, Crazzolara R, Fiegl M, Raivio T, Janne O A, Geley S, Meister B, Kofler R
Identification of glucocorticoid-response genes in children with acute lymphoblastic leukemia.
Blood. 2006 107(5):2061-2069.

  Wandke C, Geley S
Generation and characterization of an hKid-specific monoclonal antibody
Hybridoma. 2006 Feb;25(1):41-3.

  Wolf F, Geley S
A simple and stable autofocusing protocol for long multidimensional live cell microscopy.
J Microsc. 2006 Jan;221(Pt 1):72-7.

  Teis D, Kurzbauer R, Hilber D, Erlacher M, Villunger A, Geley S, Bohn G, Klein C, Hess M, Huber L
The p14/MP1-scaffold complex is required for endosomal ERK activation and cell cycle progression in vivo
submitted

  Ausserlechner M, Obexer P, Geley S, Kofler R
G1 arrest by P16INK4A uncouples growth from cell cycle progression in leukemia cells with deregulated cyclin E and c-myc expression.
Leukemia 19:1051-1057.

  Riml S, Schmidt S, Ausserlechner M, Geley S, Kofler R
Glucocorticoid receptor heterozygosity combined with lack of receptor auto-induction causes glucocorticoid resistance in Jurkat acute lymphoblastic leukemia cells.
Cell Death Differ. 2004 Jul;11 Suppl 1:S65-72.

  Ausserlechner M, Obexer P, Böck G, Geley S, Kofler R
Cyclin D3 and c-myc control glucocorticoid-induced cell cycle arrest but not apoptosis in lymphoblastic leukemia cells.
Cell Death Differ. 11:165-174.

  Riml S, Schmidt S, Ausserlechner M, Geley S, Kofler R
Glucocorticoid receptor heterozygosity combined with lack of receptor auto-induction causes glucocorticoid resistance in Jurkat acute lymphoblastic leukemia cells.
Cell Death Differ. 11 Suppl 1:S65-S72.

  Tzankov A, Zimpfer A, Lugli A, Krugmann J, Went P, Schraml P, Maurer R, Ascani S, Pileri S, Geley S, Dirnhofer S (2003)
High-throughput tissue microarray analysis of G1- cyclin alterations in classical Hodgkin's lymphoma indicates overexpression of cyclin E1
J Pathol 199:201-207. 2003