About the group
Colorectal cancer is one of the leading causes of cancer related death in Hungary and in the Western countries. Despite the progress in understanding colorectal tumorigenesis, this disease still represents an outstanding health problem.
Our mission is to identify novel targetable genes and mechanisms that can form the basis of future therapeutic interventions for colorectal cancer.
At least 50% of the Western population develops a colorectal tumor by the age of 70, and in about 1 in 10 of these individuals, progression to malignancy ensues. The estimated lifetime risk of developing colorectal cancer (CRC) is thus approximately 5-6%. As a result, CRC is one of the leading causes of cancer related morbidity and mortality in Hungary.
The intestinal epithelium is continuously renewed by a small proliferating stem cell population, residing at the bottom of intestinal crypts. Importantly, some cellular hierarchy can be observed not only in normal wild type tissues, but also in the mutant, malignant tissues, and tumor cells differ in their proliferating and invading potentials -a small tumor cell population possesses self-renewing and multilineage differentiation potential, typical features of stem cells.
Our research intends to identify novel mechanisms involved in CRC pathogenesis, focusing on stem-like cells, that can serve as potential novel therapeutic targets, which is a compelling need based on the high incidence rate and malignancy of CRC. We study novel molecules with not-well known function in CRC and novel mechanisms of the cross-communication between tumor cells and the stroma, such as extracellular vesicles.
Extracellular vesicles (EVs) represent a heterogenous group of lipid bilayer enclosed vesicles released by cells. They transfer a wide array of biologically important molecules, such as proteins, lipids, mRNAs, miRNAs and DNA when they target the recipient cells, thus representing a novel way a cell-cell communication.
We use a large array of state-of-the-art methods to answer our biological questions, such as the organoid technology and the genome editing CRISPR-Cas9 method. Unlike the traditional cell lines, the three dimensional organoid cultures maintain the cellular heterogeneity similar to the in vivo tissues, such as tumors. They can be genetically manipulated ex vivo, providing an excellent and well-controlled, improved experimental system to dissect the underlying mechanism of diseases. The CRISPR-Cas9 technology enables the rapid and targeted modifications of the genome, such as introducing inactivating mutations into genes, inserting or replacing specific sequences.
Our research group is financed by the Starting Grant of the Semmelweis University, Faculty of Medicine, by the OTKA-NN and NVKP_16 Grants of the National Research, Development and Innovation Office (Hungary) and by ICGEB-CRP Early Career Return Grant.
||Andrea Kelemen, MSc student
||Ádám Oszvald, PhD student (co-supervision with Prof. Edit Buzás)
Kivelä R, Salmela I, Nguyen YH, Petrova TV, Koistinen HA, Wiener Z, Alitalo K (2016). The transcription factor Prox1 is essential for satellite cell differentiation and muscle fibre-type regulation. Nat Commun, 7, 13124. IF: 11,329.
Sodar B, Kittel A, Paloczi K, Vukman K, Osteikoetxea X, Szabó-Taylor K, Nemeth A, Sperlágh B, Baranyai T, Giricz Z, Wiener Z, Turiak L, Drahos L, Pallinger E, Vekey K, Ferdinandy P, Falus A, Buzas EI (2016). Low-density lipoprotein mimics blood plasma-derived exosomes and microvesicles during isolation and detection. Sci Rep, 6, 24316. IF: 5.578
- Tamminen K, Balboa D, Toivonen S, Pakarinen MP, Wiener Z, Alitalo K, Otonkoski T (2015). Intestinal Commitment and Maturation of Human Pluripotent Stem Cells Is Independent of Exogenous FGF4 and R-spondin1. PLoS One, 10, e0134551. IF: 3.234
- Szmolka A, Wiener Z, Matulova ME, Varmuzova K, Rychlik I (2015). Gene Expression Profiles of Chicken Embryo Fibroblasts in Response to Salmonella Enteritidis Infection. PLoS One, 10, e0127708. IF: 3.234
- Wiener Z, Högström J, Hyvönen V, Band AM, Kallio P, Holopainen T, Dufva O, Haglund C, Kruuna O, Oliver G, Ben-Neriah Y, Alitalo K (2014). Prox1 promotes expansion of the colorectal cancer stem cell population to fuel tumor growth and ischemia resistance. Cell Rep, 8, 1943-56. IF: 8.358
- Wiener Z, Band AM, Kallio P, Högström J, Hyvönen V, Kaijalainen S, Ritvos O, Haglund C, Kruuna O, Robine S, Louvard D, Ben-Neriah Y, Alitalo K (2014). Oncogenic mutations in intestinal adenomas regulate Bim-mediated apoptosis induced by TGF-β. Proc Natl Acad Sci USA, 111, E2229-36. IF: 9.674
- Gilicze AB, Wiener Z, Tóth S, Buzás E, Pállinger E, Falcone FH, Falus A (2014). Myeloid-Derived microRNAs, miR-223, miR27a, and miR-652, Are Dominant Players in Myeloid Regulation. Biomed Res Int. 2014:870267. Review. IF: 1.579
- Pribluda A, Elyada E, Wiener Z, Hamza H, Goldstein RE, Biton M, Burstain I, Morgenstern Y, Brachya G, Billauer H, Biton S, Snir-Alkalay I, Vucic D, Schlereth K, Mernberger M, Stiewe T, Oren M, Alitalo K, Pikarsky E, Ben-Neriah Y (2013). A senescence-inflammatory switch from cancer-inhibitory to cancer-promoting mechanism. Cancer Cell, 24, 242-56. IF: 23.893
- Holopainen T, López-Alpuche V, Zheng W, Heljasvaara R, Jones D, He Y, Tvorogov D, D'Amico G, Wiener Z, Andersson LC, Pihlajaniemi T, Min W, Alitalo K (2012). Deletion of the endothelial Bmx tyrosine kinase decreases tumor angiogenesis and growth. Cancer Res, 72, 3512-21. IF: 8.650
- Molnár V, Érsek B, Wiener Z, Tömböl Z, Szabó PM, Igaz P, Falus A (2012). MicroRNA-132 targets HB-EGF upon IgE-mediated activation in murine and human mast cells. Cell Mol Life Sci, 69, 793-808. IF: 5.615
- Elyada E, Pribluda A, Goldstein RE, Morgenstern Y, Brachya G, Cojocaru G, Snir-Alkalay I, Burstain I, Haffner-Krausz R, Jung S, Wiener Z, Alitalo K, Oren M, Pikarsky E, Ben-Neriah Y (2011). CKIα ablation highlights a critical role for p53 in invasiveness control. Nature, 470, 409-13. IF: 36.280
- Szabó PM, Wiener Z, Tömböl Z, Kovács A, Pócza P, Horányi J, Kulka J, Riesz P, Tóth M, Patócs A, Gaillard RC, Falus A, Rácz K, Igaz P (2009). Differences in the expression of histamine-related genes and proteins in normal human adrenal cortex and adrenocortical tumors. Virchows Arch, 455, 133-42. IF: 2.305
- Tölgyesi G, Molnár V, Semsei AF, Kiszel P, Ungvári I, Pócza P, Wiener Z, Komlósi ZI, Kunos L, Gálffy G, Losonczy G, Seres I, Falus A, Szalai C (2009). Gene expression profiling of experimental asthma reveals a possible role of paraoxonase-1 in the disease. Int Immunol, 21, 967-75. IF: 3.403
- Tömböl Z, Szabó P, Molnár V, Wiener Z, Tölgyesi G, Horànyi J, Riesz P, Reismann P, Patócs A, Likó I, Gaillard R, Falus A, Racz K, Igaz P (2009). Integrative molecular-bioinformatics study of human adrenocortical tumors: microRNA, tissue specific target prediction and pathway analysis. Endocr Relat Cancer, 16, 895-906. IF: 4.282
- Wiener Z, Pocza P, Racz M, Nagy G, Tolgyesi G, Molnar V, Jaeger J, Buzas E, Gorbe E, Papp Z, Rigo J, Falus A (2008). IL-18 induces a marked gene expression profile change and increased Ccl1 (I-309) production in mouse mucosal mast cell homologs. Int Immunol. 20: 1565-73. IF: 3.181
- Molnar V, Tamasi V, Bakos B, Wiener Z, Falus A (2008). Changes in miRNA expression in solid tumors: An miRNA profiling in melanomas. Semin Cancer Biol. 18: 111-22. IF: 8.284
- György B, Tóthfalusi L, Nagy G, Pásztói M, Géher P, Lörinc Z, Polgár A, Rojkovich B, Ujfalussy I, Poór G, Pócza P, Wiener Z, Misják P, Koncz A, Falus A, Buzás EI (2008). Natural autoantibodies reactive with glycosaminoglycans in rheumatoid arthritis. Arthritis Res Ther. 10, R110. IF: 4.485
- Pos Z, Wiener Z, Pocza P, Racz M, Toth S, Darvas Z, Molnar V, Hegyesi H, Falus A (2008). Histamine suppresses fibulin-5 and insulin-like growth factor-II receptor expression in melanoma. Cancer Res 68:1997-2005. IF: 7.514
- Gilicze A, Kohalmi B, Pocza P, Keszei M, Jaeger J, Gorbe E, Papp Z, Toth S, Falus A, Wiener Z (2007). HtrA1 is a novel mast cell serine protease of mice and men. Mol Immunol. 44, 2961-8. IF: 3.742
- Wiener Z, Kohalmi B, Pocza P, Jeager J, Tolgyesi G, Toth S, Gorbe E, Papp Z, Falus A (2007). The immunoregulatory TIM-3 is expressed in melanoma cells and is upregulated in TGF-beta stimulated mast cells. J Invest Dermatol. 127, 906-14. IF: 4.829
- Igaz P, Wiener Z, Szabo P, Falus A, Gaillard RC, Horanyi J, Racz K, Tulassay Z (2006). Functional genomics approaches for the study of sporadic adrenal tumor pathogenesis: Clinical implications. J Steroid BiochemMol Biol 101, 87-96. Review. IF: 2.825
- Wiener Z, Ontsouka EC, Jakob S, Torgler R, Falus A, Mueller C, Brunner T (2004). Synergistic induction of the Fas (CD95) ligand promoter by Max and NFkappaB in human non-small lung cancer cells. Exp Cell Res 299, 227-35. IF: 4.007
- Wiener Z, Falus A, Toth S (2004). IL-9 increases the expression of several cytokines in activated mast cells, while the IL9 induced IL-9 production is inhibited in mast cells of histamine-free transgenic mice. Cytokine 26, 122-30. IF: 1.986
- Wiener Z, Andrásfalvy M, Pállinger E, Kovács P, Szalai Cs, Erdei A, Toth S, Nagy A, Falus A (2002). Bone marrow-derived mast cell differentiation is strongly reduced in histidine decarboxylase knockout, histamine-free mice. Int Immunol, 14, 381-87. IF: 3.595
- Prof. Kari Alitalo, Research Programs Unit and the Wihuri Research Institute, University of Helsinki, Finland
- Prof. Olli Ritvos, Department of Bacteriology, Haartman Institute, University of Helsinki, Finland
- Dr. Csaba Ortutay, HiDucator Ltd, Tampere, Finland
- Dr. Pekka Katajisto, Institute of Biotechnology, University of Helsinki, Finland
- Prof. Timo Otonkoski, Research Programs Units, University of Helsinki, Finland
- Prof. László Harsányi, 1st Department of Surgery, Semmelweis University, Budapest, Hungary