Awards:
2024- Joseph Cours Scholarship
2022- award from the Bodzsár Éva Foundation (Eötvös Loránd University)
2020- Török József award (in recognition of outstanding research and academic achievements, University
Posters & Presentations & workshops:
2025- Hungarian Molecular Life Sciences – Eger – poster (https://2025.
2023- Hungarian Molecular Life Sciences – Eger – poster (https://2023.
2022- 8th meeting of the invadosome consortium, Séte, France - poster & flash poster presentation (
2022- Zebrafish xenograft course, Lisbon, Portugalia
2022- HADDOCK workshop, Budapest
2022 - Annual Meeting of the Hungarian Biochemical Society- Pécs- presentation (
2021- Hungarian Molecular Life Sciences – Eger – poster (https://2021.
EDUCATION
2020-2025: PhD (Doctoral School of Biology, Eötvös Loránd University)
2018-2020: MSc in Molecular Biology (University of Debrecen)
2014-2018: BSc in Medical Laboratory and Diagnostic Imaging Analyst (University of Debrecen)
RESEARCH, TEACHING, or OTHER INTERESTS
Cancer Research, Cell Biology, Molecular Biology, Biochemistry, Genetics and Molecular Biology
10
Scopus Publications
Scopus Publications
The sweet and the bitter sides of galectin-1 in immunity: its role in immune cell functions, apoptosis, and immunotherapies for cancer with a focus on T cells Julianna Novák, Tamás Takács, Álmos Tilajka, Loretta László, Orsolya Oravecz, Emese Farkas, Nándor Gábor Than, László Buday, Andrea Balogh, Virág Vas Seminars in Immunopathology, 2025 Galectin-1 (Gal-1), a member of the β-galactoside-binding soluble lectin family, is a double-edged sword in immunity. On one hand, it plays a crucial role in regulating diverse immune cell functions, including the apoptosis of activated T cells. These processes are key in resolving inflammation and preventing autoimmune diseases. On the other hand, Gal-1 has significant implications in cancer, where tumor cells and the tumor microenvironment (TME) (e.g., tumor-associated fibroblasts, myeloid-derived suppressor cells) secrete Gal-1 to evade immune surveillance and promote cancer cell growth. Within the TME, Gal-1 enhances the differentiation of tolerogenic dendritic cells, induces the apoptosis of effector T cells, and enhances the proliferation of regulatory T cells, collectively facilitating tumor immune escape. Therefore, targeting Gal-1 holds the potential to boost anti-tumor immunity and improve the efficacy of cancer immunotherapy. This review provides insights into the intricate role of Gal-1 in immune cell regulation, with an emphasis on T cells, and elucidates how tumors exploit Gal-1 for immune evasion and growth. Furthermore, we discuss the potential of Gal-1 as a therapeutic target to augment current immunotherapies across various cancer types.
Integrative analysis of RAS signaling effectors reveals stage-dependent oncogenic patterns in colon adenocarcinoma Loretta László, Anna Lovrics, Álmos Tilajka, Tamás Takács, László Buday, Virag Vas Biotechnology Reports, 2025 Cancer rarely results from a single gene defect but emerges from disruptions in complex cellular networks. The Network Medicine perspective guides our investigation of cancer-driving interactions, particularly focusing on RAS signaling pathways that are key mediator for cancer development. We analyzed gene expression patterns in colon and lung cancers to identify stage-specific molecular drivers. Using computational modelling combined with patient tissue analysis, we discovered five key genes that are specifically altered in early-stage colon cancer: RAF1, PLCE1, RGL1, RIN1, and GRB7. These genes work as RAS effectors in signaling and can effectively distinguish between normal and cancerous colon tissue. Our approach combines network analysis with gene expression studies to understand how RAS signaling disruption contributes to colon cancer development. These findings suggest that targeting early-stage RAS-related changes could offer therapeutic opportunities before cancer becomes more complex and harder to treat.
Insulin receptor substrate 1 is a novel member of EGFR signaling in pancreatic cells Tamás Takács, Loretta László, Álmos Tilajka, Julianna Novák, László Buday, Virag Vas European Journal of Cell Biology, 2024 Pancreatic ductal adenocarcinoma is an extremely incurable cancer type characterized by cells with highly proliferative capacity and resistance against the current therapeutic options. Our study reveals that IRS1 acts as a bridging molecule between EGFR and IGFR/InsR signalization providing a potential mechanism for the interplay between signaling pathways and bypassing EGFR-targeted or IGFR/InsR-targeted therapies. The analysis of IRS1 phosphorylation status in four pancreatic cell lines identified the impact of EGFR signaling on IRS1 activation in comparison with InsR/IGFR signaling. Significantly reduced viability was observed in IRS1-silenced cells even upon EGF stimulation showing the critical role of IRS1 in the EGFR signaling network in both malignant and normal pancreatic cells. This study also demonstrated that EGFR binds directly to IRS1 and at least on two tyrosine sites, Y612 and Y896, IRS1 becomes phosphorylated in response to EGF stimulation. Mechanistically, the EGFR-mediated phosphorylation of IRS1 can further activate the MAPK signaling pathway with the recruitment of GRB2 protein. Collectively, in this study, IRS1 was identified as a crucial regulator in the EGFR signaling suggesting IRS1 as a potential target for more durable responses to targeted PDAC therapy. • EGF induces IRS1 phosphorylation at the Y612 and Y898 positions in cancerous and normal pancreatic cells. • IRS1 is necessary for EGF-induced enhanced proliferation via GRB2 recruitment and MAPK signaling activation. • EGFR directly interacts with IRS1 in pancreatic cells upon EGF stimulation. • IRS1 is a bridging molecule between EGFR and IGFR/InsR signaling, and redundant signalization between these pathways contributes to the high proliferative potential of pancreatic cells.
Unveiling epithelial plasticity regulation in lung cancer: Exploring the cross-talk among Tks4 scaffold protein partners Loretta László, Anita Kurilla, Álmos Tilajka, Rita Pancsa, Tamás Takács, Julianna Novák, László Buday, Virag Vas Molecular Biology of the Cell, 2024 The epithelial-to-mesenchymal transition (EMT) represents a hallmark event in the evolution of lung cancer. This work aims to study a recently described EMT-regulating protein, Tks4, and to explore its potential as a prognostic biomarker in non–small cell lung cancer. In this study, we used CRISPR/Cas9 method to knockout (KO) Tks4 to study its functional roles in invadopodia formation, migration, and regulation of EMT marker expressions and we identified Tks4-interacting proteins. Tks4-KO A549 cells exhibited an EMT-like phenotype characterized by elongated morphology and increased expression of EMT markers. Furthermore, analyses of a large-scale lung cancer database and a patient-derived tissue array data revealed that the Tks4 mRNA level was decreased in more aggressive lung cancer stages. To understand the regulatory role of Tks4 in lung cancer, we performed a Tks4-interactome analysis via Tks4 immunoprecipitation-mass spectrometry on five different cell lines and identified CAPZA1 as a novel Tks4 partner protein. Thus, we propose that the absence of Tks4 leads to disruption of a connectome of multiple proteins and that the resulting undocking and likely mislocalization of signaling molecules impairs actin cytoskeleton rearrangement and activates EMT-like cell fate switches, both of which likely influence disease severity.
Predictive value analysis of the interaction network of Tks4 scaffold protein in colon cancer Álmos Tilajka, Anita Kurilla, Loretta László, Anna Lovrics, Julianna Novák, Tamás Takács, László Buday, Virag Vas Frontiers in Molecular Biosciences, 2024 BackgroundColorectal carcinoma (CRC) has emerged as one of the most widespread cancers and was the third leading cause of cancer-related mortality in 2020. The role of the podosomal protein Tks4 in tumor formation and progression is well established, including its involvement in gastric carcinoma and hepatocellular carcinoma; however, exploration of Tks4 and its associated EMT-regulating interactome in the context of colon cancer remains largely unexplored.MethodsWe conducted a comprehensive bioinformatic analysis to investigate the mRNA and protein expression levels of Tks4 and its associated partner molecules (CD2AP, GRB2, WASL, SRC, CTTN, and CAPZA1) across different tumor types. We quantified the expression levels of Tks4 and its partner molecules using qPCR, utilizing a TissueScan colon cancer array. We then validated the usefulness of Tks4 and its associated molecules as biomarkers via careful statistical analyses, including Pearson’s correlation analysis, principal component analysis (PCA), multiple logistic regression, confusion matrix analysis, and ROC analysis.ResultsOur findings indicate that the co-expression patterns of the seven examined biomarker candidates better differentiate between tumor and normal samples compared with the expression levels of the individual genes. Moreover, variable importance analysis of these seven genes revealed four core genes that yield consistent results similar to the seven genes. Thus, these four core genes from the Tks4 interactome hold promise as potential combined biomarkers for colon adenocarcinoma diagnosis and prognosis.ConclusionOur proposed biomarker set from the Tks4 interactome shows promising sensitivity and specificity, aiding in colon cancer prevention and diagnosis.
Studying the Association of TKS4 and CD2AP Scaffold Proteins and Their Implications in the Partial Epithelial–Mesenchymal Transition (EMT) Process Anita Kurilla, Loretta László, Tamás Takács, Álmos Tilajka, Laura Lukács, Julianna Novák, Rita Pancsa, László Buday, Virág Vas International Journal of Molecular Sciences, 2023 Colon cancer is a leading cause of death worldwide. Identification of new molecular factors governing the invasiveness of colon cancer holds promise in developing screening and targeted therapeutic methods. The Tyrosine Kinase Substrate with four SH3 domains (TKS4) and the CD2-associated protein (CD2AP) have previously been linked to dynamic actin assembly related processes and cancer cell migration, although their co-instructive role during tumor formation remained unknown. Therefore, this study was designed to investigate the TKS4-CD2AP interaction and study the interdependent effect of TKS4/CD2AP on oncogenic events. We identified CD2AP as a novel TKS4 interacting partner via co-immunoprecipitation-mass spectrometry methods. The interaction was validated via Western blot (WB), immunocytochemistry (ICC) and proximity ligation assay (PLA). The binding motif of CD2AP was explored via peptide microarray. To uncover the possible cooperative effects of TKS4 and CD2AP in cell movement and in epithelial-mesenchymal transition (EMT), we performed gene silencing and overexpressing experiments. Our results showed that TKS4 and CD2AP form a scaffolding protein complex and that they can regulate migration and EMT-related pathways in HCT116 colon cancer cells. This is the first study demonstrating the TKS4-CD2AP protein–protein interaction in vitro, their co-localization in intact cells, and their potential interdependent effects on partial-EMT in colon cancer.
A Novel Cell-Based Model for a Rare Disease: The Tks4-KO Human Embryonic Stem Cell Line as a Frank-Ter Haar Syndrome Model System Loretta László, Hédi Maczelka, Tamás Takács, Anita Kurilla, Álmos Tilajka, László Buday, Virag Vas, Ágota Apáti International Journal of Molecular Sciences, 2022 Tyrosine kinase substrate with four SH3 domains (Tks4) scaffold protein plays roles in cell migration and podosome formation and regulates systemic mechanisms such as adult bone homeostasis and adipogenesis. Mutations in the Tks4 gene (SH3PXD2b) cause a rare developmental disorder called Frank-Ter Haar syndrome (FTHS), which leads to heart abnormalities, bone tissue defects, and reduced adiposity. We aimed to produce a human stem cell-based in vitro FTHS model system to study the effects of the loss of the Tks4 protein in different cell lineages and the accompanying effects on the cell signalome. To this end, we used CRISPR/Cas9 (clustered, regularly interspaced, short palindromic repeats (CRISPR)/CRISPR associated (Cas9)) to knock out the SH3PXD2b gene in the HUES9 human embryonic stem cell line (hESC), and we obtained stable homo- and heterozygous knock out clones for use in studying the potential regulatory roles of Tks4 protein in embryonic stem cell biology. Based on pluripotency marker measurements and spontaneous differentiation capacity assays, we concluded that the newly generated Tks4-KO HUES9 cells retained their embryonic stem cell characteristics. We propose that the Tks4-KO HUES9 cells could serve as a tool for further cell differentiation studies to investigate the involvement of Tks4 in the complex disorder FTHS. Moreover, we successfully differentiated all of the clones into mesenchymal stem cells (MSCs). The derived MSC cultures showed mesenchymal morphology and expressed MSC markers, although the expression levels of mesodermal and osteogenic marker genes were reduced, and several EMT (epithelial mesenchymal transition)-related features were altered in the Tks4-KO MSCs. Our results suggest that the loss of Tks4 leads to FTHS by altering cell lineage differentiation and cell maturation processes, rather than by regulating embryonic stem cell potential.
Novel roles of sh2 and sh3 domains in lipid binding Szabolcs Sipeki, Kitti Koprivanacz, Tamás Takács, Anita Kurilla, Loretta László, Virag Vas, László Buday Cells, 2021 Signal transduction, the ability of cells to perceive information from the surroundings and alter behavior in response, is an essential property of life. Studies on tyrosine kinase action fundamentally changed our concept of cellular regulation. The induced assembly of subcellular hubs via the recognition of local protein or lipid modifications by modular protein interactions is now a central paradigm in signaling. Such molecular interactions are mediated by specific protein interaction domains. The first such domain identified was the SH2 domain, which was postulated to be a reader capable of finding and binding protein partners displaying phosphorylated tyrosine side chains. The SH3 domain was found to be involved in the formation of stable protein sub-complexes by constitutively attaching to proline-rich surfaces on its binding partners. The SH2 and SH3 domains have thus served as the prototypes for a diverse collection of interaction domains that recognize not only proteins but also lipids, nucleic acids, and small molecules. It has also been found that particular SH2 and SH3 domains themselves might also bind to and rely on lipids to modulate complex assembly. Some lipid-binding properties of SH2 and SH3 domains are reviewed here.
Recent updates on the significance of kras mutations in colorectal cancer biology Loretta László, Anita Kurilla, Tamás Takács, Gyöngyi Kudlik, Kitti Koprivanacz, László Buday, Virag Vas Cells, 2021 The most commonly mutated isoform of RAS among all cancer subtypes is KRAS. In this review, we focus on the special role of KRAS mutations in colorectal cancer (CRC), aiming to collect recent data on KRAS-driven enhanced cell signalling, in vitro and in vivo research models, and CRC development-related processes such as metastasis and cancer stem cell formation. We attempt to cover the diverse nature of the effects of KRAS mutations on age-related CRC development. As the incidence of CRC is rising in young adults, we have reviewed the driving forces of ageing-dependent CRC.
