Dr Sabine Wimmer-Kleikamp
E:
T: +61 2 9036 3056
F: +61 2 9036 3038
K25 - Medical Foundation Building
The University of Sydney
NSW 2006 Australia
Position
NHMRC CJ Martin Fellow, Head of the cellular imaging group
Education/Employment
| 2004 | PhD, Melbourne University, Ludwig Institute for Cancer Research |
| 2004-2006 | Postdoc, Department of Biochemistry, Monash University; Cancer Council of Australia Postdoctoral Fellow |
| 2006-2008 | NHMRC CJ Martin Fellow, EMBL in Heidelberg, Germany |
| 2008-present | NHMRC CJ Martin Fellow, Centre for Vascular Research, University of Sydney, Stocker lab |
| 2008-present | Conjoint Lecturer, The University of New South Wales, Faculty of Medicine |
Research interests
Cell to cell signalling events, high end imaging technologies
Recent results in collaboration with others
- Developed a novel FLIM-based assay that allows for the first time to document and quantify conformational changes of trans- membrane proteins in intact cells
- Established imaging of Quantum dot tagged cell surface proteins by correlative light microscopy and Electron microscopy tomography
- Eph RTK-associated PTP activities control receptor phosphorylation levels, and as a result also switch the response to ephrin-contact from repulsion to adhesion in cancer cells
Collaborators
- Dr Achilleas Frangakis, EMBL Heidelberg, Germany
- Associate Professor Fawaz Haj, University of California, Davis, USA
- Professor Philippe Bastiaens, Max Planck Institute for Physiology, Dortmund, Germany
- Associate Professor Martin Lackmann, Monash University, Melbourne Australia
- Professor Wendy Jessup, University of New South Wales, Sydney, Australia
- Associate Professor Len Kritharides, University of Sydney & University of New South Wales, Sydney, Australia
PhD or Honours project opportunity: Imaging redox regulation of cellular signaling systems
This project will develop advanced imaging assays to study temporal and spatial dynamics of redox processes in live cells.
Receptor tyrosine kinases regulate key cellular processes like cell migration, differentiation and proliferation. Abnormal signaling of many family members of kinases has been linked to diseases, such as cancer and vascular disease. Growth factor binding induces receptor oligomerization at the plasma membrane, leading to the activation of receptor tyrosine kinases, and auto trans-phosphorylation of intracellular tyrosine residues. Protein-tyrosine phosphatases regulate receptor tyrosine kinase signaling: they suppress the basal activity of receptor tyrosine kinases and modulate ligand-stimulated signaling. This interplay between activation of receptor tyrosine kinases and inhibition of protein tyrosine phosphatases is regulated tightly by redox-dependent posttranslational protein modifications. However, for many signaling systems, the molecular mechanism underlying such regulation remains elusive.
The aim of this project is to identify oxidants and enzymes that affect the redox state and redox processes following receptor tyrosine kinase activation on endothelial cells. We will approach this question from both a cellular biology and biochemical perspective and test the functional relevance of our findings in experimental animal models. This project will provide a better understanding of these complex processes that may allow the development of novel therapies to target abnormal redox-modulated pathways in disease.
- Wimmer-Kleikamp SH, Janes PW, Frangakis AS, Treble K, Griesshaber B, Sabet O, Grabenbauer M, Ting AY, Saftig P, Bastiaens PI, Lackmann M. Cytoplasmic relaxation of active Eph controls ephrin shedding by ADAM10. PLoS Biol. 2009 Oct;7(10)
- Kockx M, Guo DL, Traini M, Gaus K, Kay J, Wimmer-Kleikamp S, Rentero C, Burnett JR, Le Goff W, Van Eck M, Stow JL, Jessup W, Kritharides L. Cyclosporin A decreases apolipoprotein E secretion from human macrophages via a protein phosphatase 2B-dependent and ATP-binding cassette transporter A1 (ABCA1)-independent pathway. J Biol Chem. 2009 Sep 4;284(36):24144-54.
- Wimmer-Kleikamp SH*, Nievergall E*, Janes PW, To C., Kravets L, Boyd AW and Lackmann M. Elevated protein tyrosine phosphatase activity provokes Eph/ephrin-facilitated adhesion of pre-B leukemia cells. (2008), BLOOD, 2008 Aug 1;112(3):455-6
- Janes, P.W., Saha, N., Barton WA, Kolev MV, Wimmer-Kleikamp, S.H., Nievergall E, Blobel, C.P., Himanen, J-P., Lackmann, M., Nikolov DB (2005). Adam meets Eph: an ADAM substrate recognition module acts as a molecular switch for ephrin cleavage in trans. Cell. 2005 Oct 21;123(2):185-7.
- Wimmer-Kleikamp, S.H. and Lackmann, M., Eph-modulated cell morphology, adhesion and motility in carcinogenesis (2005), IUBMB Life. 57, 421-31.
- *Vearing C, *Lee FT., Wimmer-Kleikamp SH, Spirkoska V, To C., Stylianou C, Boyd, AW, *Scott AS and *Lackmann M. (2005). Concurrent binding of anti-EphA3 antibody and ephrin-A5 amplifies EphA3 signalling and downstream responses: potential as EphA3-specific tumor targeting reagents. Cancer Research. 65, 6745-54.
- Wimmer-Kleikamp SH, Janes PW, Squire A., Bastiaens PI and Lackmann M. (2004). Recruitment of Eph receptors into signalling clusters does not require ephrin contact. J Cell Biol 164, 661-6.
- Coulthard MG, Duffy S, Down M, Evans B, Power M, Smith F, Stylianou C, Kleikamp S, Oates A, Lackmann M, Burns GF, Boyd AW (2002). The role of the Eph-ephrin signalling system in the regulation of developmental patterning Int J Dev Biol. 46: 375-384.
- Wimmer-Kleikamp SH*, Lawrenson ID*, Lock P, Schoenwaelder SM, Down M, Boyd AW, Alewood PF, Lackmann M. (2002). Ephrin-A5 induces rounding, blebbing and de-adhesion of EphA3-expressing 293T and melanoma cells by CrkII and Rho-mediated signalling. J Cell Sci. 115: 1059-1072.
