Workgroup: Mgr. Vítězslav Bryja Ph.D.
Keywords
Wnt signaling, non-canonical Wnt signaling pathway, proteomics, Dishevelled, β-arrestin
Points of interest
Morphogenetic proteins from the Wnt family are crucial regulators of embryonal development and homeostasis in the adult organism. Wnt pathway deregulation often leads to the tumor formation and is implicated in the pathogenesis of many other diseases. Despite the generally accepted importance of the Wnt pathway in disease, surprisingly few details of the molecular mechanisms of the Wnt pathway are known. Wnts bind membrane receptors from the Frizzled family, which transduce signal to phosphoprotein Dishevelled. At the level of Dishevelled signal is analyzed and depending on the ligand/coreceptor/cell is further transduced downstream via one of at least four signalling pathways. Molecular mechanisms, which directs signal at the level of Dishevelled are unknown. Our lab focuses on understanding of the crucial events between the receptor, Dishevelled and downstream pathway components. We are trying to apply our findings directly to clinically relevant problems eg. pathogenesis of cancer or leukemia. We hope that our findings will become a basis for the identification of novel therapeutic targets in cancers caused by Wnt pathway deregulation.
Methods
In order to study Wnt signalling we have implemented all basic methods of biochemistry and molecular and cellular biology. We are attempting to take advantage of the possibilities of the uptodate proteomics. Crucial biochemical findings are validated in vivo in collaboration with our partner labs using worm Caenorhabditis elegans, frog Xenopus laevis and mouse as the experimental models.
Group members
Postdoc
Postgradual students
Master students
- Bc. Martin Běhal
| Bc. Martin Běhal |
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Project: |
Analysis of the novel components of non-canonical Wnt pathway. |
| e-mail: |
323453@mail.muni.cz |
| Phone: |
+420 549 49 6811 |
| Posters: | |
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- Bc. Jakub Harnoš
| Bc. Jakub Harnoš |
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Project: |
Structure-function study of two regions of Dishevelled: DEP domain and the C-terminus |
| e-mail: |
324015@mail.muni.cz |
| Phone: |
+420 549 49 6811 |
| Posters: | |
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- Bc. Pavlína Janovská
| Bc. Pavlína Janovská |
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Project: |
Novel mechanisms in the pathogenesis of chronic lymphocytic leukemia. |
| e-mail: |
324221@mail.muni.cz |
| Phone: |
+420 549 49 6811 |
| Posters: | |
publications  |
- Bc. Jana Valnohová
| Bc. Jana Valnohová |
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Project: |
The role of Dishevelled in the G2/M phase of the cell cycle. |
| e-mail: |
324136@mail.muni.cz |
| Phone: |
+420 549 49 6811 |
| Posters: | |
| publications |
Bachelor students
- Bc. Igor Greif
| Bc. Igor Greif |
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Project: |
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| e-mail: |
360722@mail.muni.cz |
| Phone: |
+420 549 49 6811 |
| Posters: | |
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- Miroslav Hutňan
| Miroslav Hutňan |
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Project: |
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| e-mail: |
394106@mail.muni.cz |
| Phone: |
+420 549 49 6811 |
| Posters: | |
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- Marek Kravec
| Marek Kravec |
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Project: |
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| e-mail: |
393260@mail.muni.cz |
| Phone: |
+420 549 49 6811 |
| Posters: | |
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- Anna Kotrbová
| Anna Kotrbová |
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Project: |
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| e-mail: |
394295@mail.muni.cz |
| Phone: |
+420 549 49 6811 |
| Posters: | |
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- Petra Paclíková
| Petra Paclíková |
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Project: |
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| e-mail: |
394465@mail.muni.cz |
| Phone: |
+420 549 49 6811 |
| Posters: | |
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- Lucie Smyčková
| Lucie Smyčková |
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Project: |
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| e-mail: |
394502@mail.muni.cz |
| Phone: |
+420 549 49 6811 |
| Posters: | |
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Alumni
- Mgr. Jan Mašek (2007-2010), diploma student - currently Institute of Molecular Genetics, Prague (laboratory of Dr. Kozmik )
- Michaela Kilander (Sept 2008 - Dec 2008), - currently PhD student at Karolinska Institute, Stockholm, Sweden (laboratory of Gunnar Schulte )
- Mgr. Alena Salašová (2007-2011) - currently PhD student at Karolinska Institutet, Stockholm, Sweden (laboratory of Ernest Arenas )
- Ing. Kateřina Tmejová (2010 - 2011)
- Mgr. Vítězslav Kříž, Ph.D.
- Archana Mishra, MSc. PhD.
- Ranjani Sri Ganji, MSc.
- Mgr. Markéta Kaucká
- Bc. Dávid Kubíček
Cooperating institutions
Karolinska Institutet, Stockholm, Sweden
Friedrich-Alexander University, Erlangen-Nürnberg, Germany
Max Planck Institute for Molecular Genetics, Berlin, Germany
Cardiff School of Biosciences, Cardiff, UK
Hubrecht Institute, Utrecht, Netherlands
National Institutes Of Health/NIDCR, Bethesda, USA
Howard Hughes Medical Institute, Ann Arbor, USA
Institute Curie, Paríž, Francie
Cedars Sinai Medical Center, Los Angeles, USA
VIB Department of Molecular and Developmental Genetics, Leuven, Belgium
Center of molecular biology and gene therapy, Interal hematooncological clinic Faculty Hospital Brno, Czech Republic
Proteomic center, Faculty of Science, University of South Bohemia, České Budějovice, Czech Republic
Department of functional genomics, Masaryk University, Brno, Czech Republic
Projects and Grants
- Spolupráce mezi Masarykovou univerzitou a Karolinska Institutet, Stockholm na poli biomedicíny (7/2012 - 6/2015), principal investigator [www]
- Molecular mechanisms of non-canonical Wnt signaling in leukemia (1/2011 - 12/2014), řesitel
- Úloha nekanonické Wnt signalizace v molekulární patogenezi chronické lymfocytární leukémie (9/2010 - 12/2014), principal investigator
- Podpora výzkumné činnosti studentů v oblasti fyziologie a imunologie živočichů v roce 2013 (1/2013 - 12/2013), principal investigator
- Function-oriented plasma membrane proteomic profiling of Chronic Lymphocytic Leukaemia (6/2011 - 5/2013), principal investigator
- Dynamics of proteins interacting with Dishevelled and their importance for Wnt signalling (1/2009 - 12/2013), principal investigator
Selected publications
- I. Cervenka, J. Wolf, J. Masek, P. Krejci, W. R. Wilcox, A. Kozubík, G. Schulte, J. Silvio Gutkind*, V. Bryja*. (2011). Mitogen activated-protein kinases promote WNT/β-catenin signaling via phosphorylation of LRP6. Mol. Cell. Biol. 31(1):179-89.
- Witte F1, Bernatik O1, Kirchner K, Masek J, Mahl A, Krejci P, Mundlos S, Schambony A, Bryja V*, Stricker S*. (2010). Negative regulation of Wnt signaling mediated by CK1-phosphorylated Dishevelled via Ror2. FASEB J. 24(7):2417-26.
- Foldynova-Trantirkova S, Sekyrova P, Tmejova K, Brumovska E, Bernatik O, Blankenfeldt W, Krejci P, Kozubik A, Dolezal T, Trantirek L*, Bryja V*. (2010). Breast cancer-specific mutations in CK1ε inhibit Wnt/β-catenin and activate the Wnt/Rac1/JNK and NFAT pathways to decrease cell adhesion and promote cell migration. Breast Cancer Res. 12(3):R30.
- Cajanek L, Ribeiro D, Liste I, Parish CL, Bryja V*, Arenas E*. (2009). Wnt/β-catenin signaling blockade promotes neuronal induction and dopaminergic differentiation in embryonic stem cells. Stem Cells. 27:2917-27.
- Bryja V*, Andersson ER, Schambony A, Esner M, Bryjova L, Biris KK, Hall AC, Kraft B, Cajanek L, Yamaguchi TP, Buckingham M, Arenas E.* (2009): The Extracellular Domain of Lrp5/6 Inhibits Non-Canonical Wnt Signaling in vivo. Mol Biol Cell. 20: 924-936. Cover article.
- V. Bryja1, A. Schambony1, L. Cajanek, I. Dominguez, E. Arenas and G. Schulte. (2008). beta-Arrestin and casein kinase 1/2 define distinct branches of non-canonical WNT signalling pathways. EMBO Rep. 9(12): 1244-50. Featured article.
- G. Schulte and V. Bryja. The Frizzled family of unconventional GPCRs. Trends Pharmacol. Sci. 28: 518-525, 2007.
- V. Bryja, D. Gradl, A. Schambony, E. Arenas1 and G. Schulte1. (2007). β-arrestin is a necessary component of Wnt/β-catenin signaling in vitro and in vivo. Proc. Natl. Acad. Sci. USA 104: 6690-6695.
- V Bryja1, G Schulte1, N Rawal, A Grahn, and E Arenas. (2007). Wnt-5a induces Dishevelled phosphorylation and dopaminergic differentiation via a CK1δ/ε-dependent mechanism. J. Cell Sci. 120: 586-595.
- V Bryja, S Bonilla and E Arenas. Derivation of mouse embryonic stem cells. Nature Protocols 1: 2082-2087, 2006.
- Chaki M, Airik R, Ghosh AK, Giles RH, Chen R, Slaats GG, Wang H, Hurd TW, Zhou W, Cluckey A, Gee HY, Ramaswami G, Hong CJ, Hamilton BA, Cervenka I, Ganji RS, Bryja V, Arts HH, van Reeuwijk J, Oud MM, Letteboer SJ, Roepman R, Husson H, Ibraghimov-Beskrovnaya O, Yasunaga T, Walz G, Eley L, Sayer JA, Schermer B, Liebau MC, Benzing T, Le Corre S, Drummond I, Janssen S, Allen SJ, Natarajan S, O'Toole JF, Attanasio M, Saunier S, Antignac C, Koenekoop RK, Ren H, Lopez I, Nayir A, Stoetzel C, Dollfus H, Massoudi R, Gleeson JG, Andreoli SP, Doherty DG, Lindstrad A, Golzio C, Katsanis N, Pape L, Abboud EB, Al-Rajhi AA, Lewis RA, Omran H, Lee EY, Wang S, Sekiguchi JM, Saunders R, Johnson CA, Garner E, Vanselow K, Andersen JS, Shlomai J, Nurnberg G, Nurnberg P, Levy S, Smogorzewska A, Otto EA, Hildebrandt F. (2012). Exome Capture Reveals ZNF423 and CEP164 Mutations, Linking Renal Ciliopathies to DNA Damage Response Signaling. Cell. 150(3): 533-48.
- M. Kaucka, K. Plevova, S. Pavlova, J. Verner, J. Prochazkova, P. Janovska, P. Krejci, J. Kotaskova, P. Ovesna, B. Tichy, Y. Brychtova, M. Doubek, A. Kozubik, J. Mayer, S. Pospisilova and V. Bryja. (2013). The planar cell polarity pathway drives pathogenesis of chronic lymphocytic leukemia by the regulation of B-lymphocyte migration. Cancer Res. 73(5):1491-1501.
- A. Soldano, Z. Okray, P. Janovska, K. Tmejova, E. Reynaud, A. Claeys, J. Yan, B. De Strooper, J.-M. Dura, V. Bryja, B. A. Hassan: The Amyloid Precursor Proteins are conserved modulators of the Wnt/PCP pathway required for robustness of axonal outgrowth. PLoS Biol. (in press)
- K. Tanneberger, A.S. Pfister, K. Brauburger, J. Schneikert, M.V. Hadjihannas, V. Kriz, G. Schulte, V. Bryja and J. Behrens. (2011). Amer1/WTX couples Wnt-induced formation of PtdIns(4,5)P2 to LRP6 phosphorylation. EMBO J. 30: 1433-1443.
- V. Bryja1, A. Schambony1, L. Cajanek, I. Dominguez, E. Arenas and G. Schulte. (2008). beta-Arrestin and casein kinase 1/2 define distinct branches of non-canonical WNT signalling pathways. EMBO Rep. 9(12): 1244-50. Featured article
- M. Andang, J. Hjerling-Leffler, A. Moliner, T.K. Lundgren, G. Castelo-Branco, E. Nanou, E. Pozas, V. Bryja, S. Halliez, H. Nishimaru, J. Wilbertz, E. Arenas, M. Koltzenburg, M. Charnay, A. El Manira, C.F. Ibanez and P. Ernfors. (2008). Histone H2AX-dependent GABAA receptor regulation of embryonic stem cell proliferation. Nature 451: 460-464.
1 equal contribution, * corresponding author
Complete publication list
Other activities
section: Insect physiology and immunology
section: Immunology
section: Cellular and molecular physiology
