Lab for Cellular and Molecular Therapy

Head of the group

György Vereb, MD, PhD, DSc

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Lab members

• Marianna Csaplár, MSc, PhD student, junior research fellow
• István Rebenku, MSc, junior research fellow
• Árpád Szöőr, MD, PhD, assistant professor
• László Ujlaky-Nagy, MD, research fellow
• Bence Gergely, MSc, PhD student 
• Lőrinc Nagy, MSc, PhD student
• Hajnalka Toldi Vágó (Mrs), technician

Former members of the group 

• Cameron Bailey Lloyd, MSc, junior research fellow
• Miklós Petrás, MD, PhD, postdoctoral fellow
• Csaba Tamás Tóth, MSc, junior research fellow
• Gábor Tóth, MD, junior research fellow
• Barbara Zsebik (Mrs), PhD, senior postdoctoral fellow

 Research

1. Major areas of interest

• Developing and optimizing novel immune therapies based on antibodies and reprogrammed immune cells
• Molecular assembly and function of CAR T-cell immune synapses
• Interactions of receptor tyrosine kinases and integrins, their role in the pathogenesis of tumors, their possible exploitation for diagnosis, prognosis and therapeutic targeting
• Developing and improving methods for regenerating corneas with limbal stem cell deficiency (in cooperation with the Department of Ophthalmology)
• Developing microscopic and other spectroscopic/cytometric methods and testing new fluorphors for the quantitative analysis of molecular interactions and signaling processes in situ in cells and tissues

2. Recent research projects

• Highlighted the organizing role of GM1-rich membrane microdomains in the signaling of IL2R, MHC, ErbB kinases and integrins, characterized their microscopic morphology and developed a ‘Dynamically structured mosaic model’ of the cell membrane.
• Revealed that inhibiting HSP90 is a viable therapeutic optin in trastuzumab resistant Her2 positive tumors.
• Pointed out the role of interaction between ErbB family kinases and integrins in the therapy resistance of various tumors.
• Characterized new CDK5 inhibitors that can serve as inhibitors of neoangiogenesis in various pathologic conditions. Showed that V-ATPase inhibition overcomes trastuzumab resistance in breast cancer (in cooperation with Prof. Angelika Vollmar's group, LMU, Munich).
• Demonstrated the cooperative effect of a nove platinum complex and TRAIL in prostate carcinoma (in cooperation with Prof. Alois Kozubík's group, Czech Academy of Sciences, Brno).
• Identified novel markers applicable for flow cytometric selection of corneal limbal stem cells that can be used for corneal regeneration in limbal deficiency. Characterized the potential of oral mucosa as donor tissue for corneal regeneration (in cooperation with Dr. Lili Takács, Department of Ophthalmology, UD)
• Revealed that cell confluence induces switching from proliferation to migratory signaling by site-selective phosphorylation of PDGF receptors on lipid raft platforms.
• Demonstrated that therapeutic tissue levels of trastuzumab and pertuzumab likely do not saturate ADCC, and therefore the combination of both antibodies at maximum clinically approved doses should be administered to patients to recruit maximum ADCC against HER2 positive tumors.

Selected publications

• Structural hierarchy in the clustering of HLA class I molecules in the plasma membrane of human lymphoblastoid cells. Damjanovich S, Vereb G, Schaper A, Jenei A, Matkó J, Starink JP, Fox GQ, Arndt-Jovin DJ, Jovin TM. Proc Natl Acad Sci U S A. 1995 14;92(4):1122-6.
• Temporally and spectrally resolved imaging microscopy of lanthanide chelates. Vereb G, Jares-Erijman E, Selvin PR, Jovin TM. Biophys J. 1998;74(5):2210-22.
• Rapid characterization of green fluorescent protein fusion proteins on the molecular and cellular level by fluorescence correlation microscopy. Brock R, Vàmosi G, Vereb G, Jovin TM. Proc Natl Acad Sci U S A. 1999 31;96(18):10123-8.
• Cholesterol-dependent clustering of IL-2Ralpha and its colocalization with HLA and CD48 on T lymphoma cells suggest their functional association with lipid rafts. Vereb G, Matkó J, Vámosi G, Ibrahim SM, Magyar E, Varga S, Szöllosi J, Jenei A, Gáspár R Jr, Waldmann TA, Damjanovich S. Proc Natl Acad Sci U S A. 2000 23;97(11):6013-8.
• Dynamic, yet structured: The cell membrane three decades after the Singer-Nicolson model. Vereb G, Szöllosi J, Matkó J, Nagy P, Farkas T, Vigh L, Mátyus L, Waldmann TA, Damjanovich S. Proc Natl Acad Sci U S A. 2003 8;100(14):8053-8.
• Hsp90 inhibitor 17-AAG reduces ErbB2 levels and inhibits proliferation of the trastuzumab resistant breast tumor cell line JIMT-1. Zsebik B, Citri A, Isola J, Yarden Y, Szöllosi J, Vereb G. Immunol Lett. 2006 15;104(1-2):146-55
• AccPbFRET: an ImageJ plugin for semi-automatic, fully corrected analysis of acceptor photobleaching FRET images. Roszik J, Szöllosi J, Vereb G. BMC Bioinformatics. 2008 19;9:346.
• Cisplatin and a potent platinum(IV) complex-mediated enhancement of TRAIL-induced cancer cells killing is associated with modulation of upstream events in the extrinsic apoptotic pathway. Vondálová Blanárová O, Jelínková I, Szöor A, Skender B, Soucek K, Horváth V, Vaculová A, Andera L, Sova P, Szöllosi J, Hofmanová J, Vereb G, Kozubík A. Carcinogenesis. 2011;32(1):42-51.
• Differentially expressed genes associated with human limbal epithelial phenotypes: new molecules that potentially facilitate selection of stem cell-enriched populations. Takács L, Tóth E, Losonczy G, Szanto A, Bähr-Ivacevic T, Benes V, Berta A, Vereb G. Invest Ophthalmol Vis Sci. 2011 10;52(3):1252-60..
• Anti-angiogenic effects of purine inhibitors of cyclin dependent kinases. Liebl J, Krystof V, Vereb G, Takács L, Strnad M, Pechan P, Havlicek L, Zatloukal M, Fürst R, Vollmar AM, Zahler S. Angiogenesis. 2011;14(3):281-91.
• Molecular interactions of ErbB1 (EGFR) and integrin-β1 in astrocytoma frozen sections predict clinical outcome and correlate with Akt-mediated in vitro radioresistance. Petrás M, Lajtos T, Friedländer E, Klekner A, Pintye E, Feuerstein BG, Szöllosi J, Vereb G. Neuro Oncol. 2013;15(8):1027-40.
• V-ATPase inhibition overcomes trastuzumab resistance in breast cancer. von Schwarzenberg K, Lajtos T, Simon L, Müller R, Vereb G, Vollmar AM. Mol Oncol. 2014 Feb;8(1):9-19. doi: 10.1016/j.molonc.2013.08.011.
• Cell confluence induces switching from proliferation to migratory signaling by site-selective phosphorylation of PDGF receptors on lipid raft platforms. Szöőr Á, Ujlaky-Nagy L, Tóth G, Szöllősi J, Vereb G. Cell Signal. 2016 Feb;28(2):81-93. doi: 10.1016/j.cellsig.2015.11.012.
• The combination of trastuzumab and pertuzumab administered at approved doses may delay development of trastuzumab resistance by additively enhancing antibody-dependent cell-mediated cytotoxicity. Tóth G, Szöőr Á, Simon L, Yarden Y, Szöllősi J, Vereb G. MAbs. 2016 Oct;8(7):1361-1370.