Vladimir Leksa

Vladimir Leksa is a senior scientist heading the research group “Cell Adhesion” within the Molecular Immunology Unit of the Institute of Hygiene and Applied Immunology at the Center for Pathophysiology, Infectiology & Immunology, Medical University of Vienna. This research group specializes in regulatory mechanisms of cell adhesion, cell migration and signal transduction. He graduated the study of biochemistry in 1995, at the Comenius University (Bratislava, Slovakia). He completed his diploma thesis investigating the mitochondrial proteolytic system in the laboratory of Professor Stefan Kuzela at the Institute of Molecular Biology of the Slovak Academy of Sciences (Bratislava, Slovakia). After a 2-year research stay at the Cancer Research Institute in Bratislava, he started his doctoral study at the Institute of Immunology (University of Vienna, Austria). He accomplished the study in 2002 in the research group of Professor Hannes Stockinger. His work, related to regulation of pericellular proteolysis, was awarded the Thesis Prize 2002 of the Austrian Society for Allergology and Immunology. Afterwards, he continued as a postdoc and later on as a senior scientist heading the above mentioned research group “Cell Adhesion”

 

Current research interest
T lymphocytes (T cells) play a key role in the adaptive immune system, the specific defence system of higher organisms. Efficient activation of T cells to execute the immune response requires concerted interactions of receptors on their plasma membrane with extracellular ligands and submembrane signaling molecules, which results in production of cytokines, clonal expansion, cell differentiation and cell migration. Similar molecular interfaces are involved also in other physiological and pathological processes such as tissue remodelling, wound healing, tumour dissemination or angiogenesis. Although there is considerable knowledge how these processes are initiated and activated, less is known about the molecular machineries of their negative regulation. Our research interest is focused on molecules underlying such control devices. In particular, our up-to-now data strongly indicate a negative regulatory function of the mannose 6-phosphate/insulin-like growth factor 2 receptor (CD222) in pericellular proteolysis, cell migration and signal transduction. In our research, we address mechanisms and functions associated to this receptor.

 

Grants

Current
2010-2013 The Integral Regulatory Role of (CD222) in T cell activation. (No. P22908); Funded by FWF - Austrian Science Fund

Previous
2006-2009 Control of inflammatory processes by CD222. (P19014); Funded by FWF - Austrian Science Fund
2005-2007 The Mannose-6-Phosphate Receptor as the regulator of fibrinolysis on the cell surface. (APVT-51–026204); funded by the Science and Technology Assistance Agency
2005-2007 Characterization of protein complex between M6P/IGF2R (CD222) and uPAR (CD87), and its role in the regulation of cell migration. (2/5119/25); funded by the Slovak Grant Agency VEGA
2006-2007 Processing of M6PR and characterization of the M6PR-derived proteolytic fragments. (SK-11-AUT-9); the Bilateral Cooperation Slovakia-Austria

 

Publications

Dissecting Mannose 6-Phosphate-Insulin-like Growth Factor 2 Receptor Complexes That Control Activation and Uptake of Plasminogen in Cells. Leksa V, Pfisterer K, Ondrovicová G, Binder B, Lakatosová S, Donner C, Schiller HB, Zwirzitz A, Mrvová K, Pevala V, Kutejová E, Stockinger H. J Biol Chem. 2012 Jun 29;287(27):22450-62.

Soluble M6P/IGF2R released by TACE controls angiogenesis via blocking plasminogen activation. Leksa V, Loewe R, Binder B, Schiller HB, Eckerstorfer P, Forster F, Soler-Cardona A, Ondrovicová G, Kutejová E, Steinhuber E, Breuss J, Drach J, Petzelbauer P, Binder BR, Stockinger H. Circ Res. 2011 Mar 18;108(6):676-85.

Sequential cooperation of CD2 and CD48 in the buildup of the early TCR signalosome. Muhammad A, Schiller HB, Forster F, Eckerstorfer P, Geyeregger R, Leksa V, Zlabinger GJ, Sibilia M, Sonnleitner A, Paster W, Stockinger H. J Immunol. 2009 Jun 15;182(12):7672-80.

The mannose 6-phosphate/insulin-like growth factor II receptor restricts the tumourigenicity and invasiveness of squamous cell carcinoma cells. Probst OC, Puxbaum V, Svoboda B, Leksa V, Stockinger H, Mikula M, Mikulits W, Mach L. Int J Cancer. 2009 Jun 1;124(11):2559-67.

Mannose 6-phosphate/insulin-like growth factor 2 receptor limits cell invasion by controlling alphaVbeta3 integrin expression and proteolytic processing of urokinase-type plasminogen activator receptor. Schiller HB, Szekeres A, Binder BR, Stockinger H, Leksa V. Mol Biol Cell. 2009 Feb;20(3):745-56.

LFA-1-mediated leukocyte adhesion regulated by interaction of CD43 with LFA-1 and CD147. Khunkaewla P, Schiller HB, Paster W, Leksa V, Cermák L, Andera L, Horejsí V, Stockinger H. Mol Immunol. 2008 Mar;45(6):1703-11.

TGF-beta-induced apoptosis in endothelial cells mediated by M6P/IGFII-R and mini-plasminogen. Leksa V, Godar S, Schiller HB, Fuertbauer E, Muhammad A, Slezakova K, Horejsi V, Steinlein P, Weidle UH, Binder BR, Stockinger H. J Cell Sci. 2005 Oct 1;118(Pt 19):4577-86.

Engagement of Na,K-ATPase beta3 subunit by a specific mAb suppresses T and B lymphocyte activation. Chiampanichayakul S, Szekeres A, Khunkaewla P, Moonsom S, Leksa V, Drbal K, Zlabinger GJ, Hofer-Warbinek R, Stockinger H, Kasinrerk W. Int Immunol. 2002 Dec;14(12):1407-14.

The N terminus of mannose 6-phosphate/insulin-like growth factor 2 receptor in regulation of fibrinolysis and cell migration. Leksa V, Godár S, Cebecauer M, Hilgert I, Breuss J, Weidle UH, Horejsí V, Binder BR, Stockinger H. J Biol Chem. 2002 Oct 25;277(43):40575-82.

Differential display of RNA from tumorigenic and nontumorigenic variants of hamster cells transformed with avian sarcoma virus. Leksa V, Altaner C. Neoplasma. 1997;44(6):337-41.

 

Patents

V. Leksa, J. Breuss, B. Binder, H. Stockinger: Modulation of uPA-mediated functions by the amino-terminal fragment of the mannose 6-Phosphate/Insulin-like Growth Factor 2 Receptor (CD222), P42481 PCT/AT03/00224 S.


Chiampanichayakul, A. Szekeres, P. Khunkaewla, S. Moonsom, V. Leksa, K. Drbal, G. Zlabinger, R. Hofer-Warbinek, W. Kasinrerk, H. Stockinger: Monoclonal anti-Na, K-ATPase-beta3 subunit antibody P-3E10 and use thereof as a therapeutic agent, PCT/AT2003/000354