Publication of the last 3 years in genomics:

1. Balogh A, Reiniger L, Hetey S, Kiraly P, Toth E, Karaszi K, Juhasz K, Gelencser Z, Zvara A, Szilagyi A, Puskas LG, Matko J, Papp Z, Kovalszky I, Juhasz C, Than NG. Decreased Expression of ZNF554 in Gliomas is Associated with the Activation of Tumor Pathways and Shorter Patient Survival. Int J Mol Sci. 2020 Aug 11;21(16):5762. doi: 10.3390/ijms21165762. PMID: 32796700; PMCID: PMC7461028.

2. Barna L, Walter FR, Harazin A, Bocsik A, Kincses A, Tubak V, Jósvay K, Zvara Á, Campos-Bedolla P, Deli MA. Simvastatin, edaravone and dexamethasone protect against kainate-induced brain endothelial cell damage. Fluids Barriers CNS. 2020 Feb 10;17(1):5. doi: 10.1186/s12987-019-0166-1. PMID: 32036791; PMCID: PMC7008534.

3. Gyukity-Sebestyén E, Harmati M, Dobra G, Németh IB, Mihály J, Zvara Á, Hunyadi-Gulyás É, Katona R, Nagy I, Horváth P, Bálind Á, Szkalisity Á, Kovács M, Pankotai T, Borsos B, Erdélyi M, Szegletes Z, Veréb ZJ, Buzás EI, Kemény L, Bíró T, Buzás K. Melanoma-Derived Exosomes Induce PD-1 Overexpression and Tumor Progression via Mesenchymal Stem Cell Oncogenic Reprogramming. Front Immunol. 2019 Oct 18;10:2459. doi: 10.3389/fimmu.2019.02459. PMID: 31681332; PMCID: PMC6813737.

4. Bencsik P, Kiss K, Ágg B, Baán JA, Ágoston G, Varga A, Gömöri K, Mendler L, Faragó N, Zvara Á, Sántha P, Puskás LG, Jancsó G, Ferdinandy P. Sensory Neuropathy Affects Cardiac miRNA Expression Network Targeting IGF-1, SLC2a-12, EIF-4e, and ULK-2 mRNAs. Int J Mol Sci. 2019 Feb 25;20(4):991. doi: 10.3390/ijms20040991. PMID: 30823517; PMCID: PMC6412859.

5. Fenteany, Gabriel* ; Gaur, Paras* ; Hegedűs, Lili ; Dudás, Kata ; Kiss, Ernő ; Wéber,Edit ; Hackler, László ; Martinek, Tamás ; Puskás, László G. ; Haracska, Lajos Multilevel structure–activity pro􀅣ling reveals multiple green tea compound familiesthat each modulate ubiquitin-activating enzyme and ubiquitination by a distinctmechanism, SCIENTIFIC REPORTS 9 : 1 Paper: 12801 , 16 p. (2019)

6. Sárközy M, Gáspár R, Zvara Á, Kiscsatári L, Varga Z, Kővári B, Kovács MG, Szűcs G, Fábián G, Diószegi P, Cserni G, Puskás LG, Thum T, Kahán Z, Csont T, Bátkai S. Selective Heart Irradiation Induces Cardiac Overexpression of the Pro- hypertrophic miR-212. Front Oncol. 2019 Jul 16;9:598. doi: 10.3389/fonc.2019.00598. PMID: 31380269; PMCID: PMC6646706.

7. Sárközy M, Gáspár R, Zvara Á, Siska A, Kővári B, Szűcs G, Márványkövi F, Kovács MG, Diószegi P, Bodai L, Zsindely N, Pipicz M, Gömöri K, Kiss K, Bencsik P, Cserni G, Puskás LG, Földesi I, Thum T, Bátkai S, Csont T. Chronic kidney disease induces left ventricular overexpression of the pro-hypertrophic microRNA-212. Sci Rep. 2019 Feb 4;9(1):1302. doi: 10.1038/s41598-018-37690-5. PMID: 30718600; PMCID: PMC6362219.

8. Csajbók ÉA, Kocsis ÁK, Faragó N, Furdan S, Kovács B, Lovas S, Molnár G, Likó I, Zvara Á, Puskás LG, Patócs A, Tamás G. Expression of GLP-1 receptors in insulin-containing interneurons of rat cerebral cortex. Diabetologia. 2019 Apr;62(4):717-725. doi: 10.1007/s00125-018-4803-z. Epub 2019 Jan 12. PMID: 30637442.

9. Hoyk Z, Tóth ME, Lénárt N, Nagy D, Dukay B, Csefová A, Zvara Á, Seprényi G, Kincses A, Walter FR, Veszelka S, Vígh J, Barabási B, Harazin A, Kittel Á, Puskás LG, Penke B, Vígh L, Deli MA, Sántha M. Cerebrovascular Pathology in Hypertriglyceridemic APOB-100 Transgenic Mice. Front Cell Neurosci. 2018 Oct 25;12:380. doi: 10.3389/fncel.2018.00380. PMID: 30410436; PMCID: PMC6209654.

10. Keller-Pinter A, Szabo K, Kocsis T, Deak F, Ocsovszki I, Zvara A, Puskas L, Szilak L, Dux L. Syndecan-4 influences mammalian myoblast proliferation by modulating myostatin signalling and G1/S transition. FEBS Lett. 2018 Sep;592(18):3139-3151. doi: 10.1002/1873-3468.13227. Epub 2018 Sep 7. PMID: 30129974; PMCID: PMC6221024.

11. Boldog, E* ; Bakken, TE* ; Hodge, RD* ; Novotny, M ; Aevermann, BD ; Baka, J ; Borde, S; Close, JL ; Diez-Fuertes, F ; Ding, SL et al.Transcriptomic and morphophysiological evidence for a specialized human corticalGABAergic cell type, NATURE NEUROSCIENCE 21 : 9 pp. 1185-1195. , 11 p. (2018)

12. Venglovecz V, Pallagi P, Kemény LV, Balázs A, Balla Z, Becskeházi E, Gál E, Tóth E, Zvara Á, Puskás LG, Borka K, Sendler M, Lerch MM, Mayerle J, Kühn JP, Rakonczay Z Jr, Hegyi P. The Importance of Aquaporin 1 in Pancreatitis and Its Relation nt he CFTR Cl^- Channel. Front Physiol. 2018 Jul 12;9:854. doi: 10.3389/fphys.2018.00854. PMID: 30050452; PMCID: PMC6052342.

13. Lipinszki, Zoltan ; Vernyik, Viktor ; Farago, Nora ; Sari, Tobias ; Puskas, Laszlo G ;Blattner, Frederick R ; Posfai, Gyorgy ; Gyorfy, Zsuzsanna, Enhancing the Translational Capacity of E. coli by Resolving the Codon Bias., ACS SYNTHETIC BIOLOGY 7 : 11 pp. 2656-2664. , 9 p. (2018)

14. Ágg B, Baranyai T, Makkos A, Vető B, Faragó N, Zvara Á, Giricz Z, Veres DV, Csermely P, Arányi T, Puskás LG, Varga ZV, Ferdinandy P. MicroRNA interactome analysis predicts post-transcriptional regulation of ADRB2 and PPP3R1 in the hypercholesterolemic myocardium. Sci Rep. 2018 Jul 4;8(1):10134. doi: 10.1038/s41598-018-27740-3. Erratum in: Sci Rep. 2018 Aug 9;8(1):12159. PMID: 29973623; PMCID: PMC6031673.

15. Brasko, C ; Smith, K ; Molnar, C ; Farago, N ; Hegedus, L ; Balind, A ; Balassa, T ;Szkalisity, A ; Sukosd, F ; Kocsis, K et al., Intelligent image-based in situ single-cell isolation, NATURE COMMUNICATIONS 9 : 1 Paper: 226 , 7 p. (2018)

Cytometry unit

The cooperation of highly specialized cell types maintains the homeostasis of multicellular organisms. The disturbance of that harmony contributes to the development of several diseases. Most of the cellular functions are executed by proteins so it is essential to investigate biological processes at the protein level. One of the routinely used methods to study cellular proteins is flow cytometry which detects cell surface or intracellular proteins by fluorescently labeled antibodies at single cell resolution. Currently, we use BC Cytoflex S (4 lasers), one BD FACSCalibur (2 lasers) analyzators and one BD Jazz (2 lasers) sorter. Overlap among the fluorescence spectra of different dyes limits the possibility of high multiplexicity in one single tube. To overcome the limitations of flow cytometry, antibodies are labeled by stable heavy metal isotopes (min 96% monoisotopic) in mass cytometry. Mass cytometer detects the distinct atomic mass of heavy metal isotopes which offers the possibility to acquire up to 42 markers in one sample. Mass cytometry is unique technology in our laboratory within Hungary. The characterization of cellular heterogeneity is achieved at the protein level with single cell resolution from homogenous cell suspensions of different biological samples (blood, solid tumors, different tissues) followed by antibody staining for mass cytometry. High content data analysis (Cytobank, Astrolabe, Maxpar Pathsetter) is also integrated in our portfolio.

We focus on the disturbances of the activation and regulation of immune system; therefore we study human patient-derived blood or tissue samples at single cell resolution. The high content immunophenotyping is performed on PBMCs or different tissues such as primary adenocarcinoma.

The comparative bioinformatic analysis of biological specimens (patients vs healthy controls) reveals differences in the expression pattern of proteins of interest at single cell resolution. To complement the investigation of PBMCs we quantify the cytokine/chemokine content of the corresponding liquid biopsies by Luminex (MagPix) or Legendplex (Biolegend) technologies. We describe expression patterns of proteins associated with a given pathology such as rheumatoid arthritis, adenocarcinoma, COPD to find diagnostic, prognostic markers or novel therapeutic targets. We develop in vitro/ex vivo functional immune assays (i) to screen drug candidate molecules, (ii) to better understand the pathomechanism and reveal signal transduction pathways behind the given pathologies.

The laboratory is run on service and collaborative basis. We have built wide national and international connections to research groups and biotech companies.

Main research areas

• Multiparametric immunophenotyping of systemic autoimmune disorders (RA, SLE, SSC)

• Single cell mass cytometric characterization of the inflammatory complications in type II diabetes mellitus

• Investigation of plasma proteins and single cell PBMCs in stable vs exacerbating COPD

• High multiplex investigation of the intratumor heterogeneity in human primary adenocarcinoma

• Studying the innate immunity in Drosophila melanogaster mutant hemocytes by single cell mass cytometry

• Analysis of the effect of drug candidate molecules using single cell mass cytometry

Publications from the last 3 years in cytomtery:

1. József Á. Balog, Viktor Honti, Éva Kurucz, Beáta Kari, László G. Puskás, István Andó, Gábor J. Szebeni, Multi-Dimensional Immuno-Profiling of Drosophila Hemocytes by Single Cell Mass Cytometry, Genomics Proteomics & Bioinformatics, accepted for publication

2. Kotogány, E.; Balog, J.Á.; Nagy, L.I.; Alföldi, R.; Bertagnolo, V.; Brugnoli, F.; Demjén, A.; Kovács, A.K.; Batár, P.; Mezei, G.; Szabó, R.; Kanizsai, I.; Varga, C.; Puskás, L.G.; Szebeni, G.J. Imidazo[1,2-b]pyrazole-7-Carboxamide Derivative Induces Differentiation-Coupled Apoptosis of Immature Myeloid Cells Such as Acute Myeloid Leukemia and Myeloid-Derived Suppressor Cells. Int. J. Mol. Sci. 2020, 21, 5135.

3. Roberta Fajka-Boja, Gábor J Szebeni, Éva Hunyadi-Gulyás, László G Puskás, Robert Katona, Polyploid adipose stem cells shift the balance of IGF1/IGFBP2 to promote the growth of breast cancer, Frontiers in Oncology, section Molecular and Cellular Oncology, 2020;10:157

4. József Á. Balog,László Hackler Jr.,Anita K. Kovács,Patrícia Neuperger,Róbert Alföldi,Lajos I. Nagy,László G. Puskás and Gábor J. Szebeni, Single Cell Mass Cytometry Revealed the Immunomodulatory Effect of Cisplatin Via Downregulation of Splenic CD44+, IL-17A+ MDSCs and Promotion of Circulating IFN-γ+ Myeloid Cells in the 4T1 Metastatic Breast Cancer Model Int. J. Mol. Sci. 2020, 21(1), 170; 

5. Alföldi R, Balog JÁ, Faragó N, Halmai M, Kotogány E, Neuperger P, Nagy LI, Fehér LZ, Szebeni GJ, Puskás LG. Single Cell Mass Cytometry of Non-Small Cell Lung Cancer Cells Reveals Complexity of In vivo And Three-Dimensional Models over the Petri-dish. Cells. 2019 Sep 16;8(9). pii: E1093. doi: 10.3390/cells8091093. Special Issue: “Single cell Analysis”

6. Gábor J. Szebeni, Lajos I. Nagy, Anikó Berkó, Alexandra Hoffmann, Liliána Z. Fehér, Mária Bagyánszki , Beáta Kari, József A. Balog, László Hackler Jr. ,Iván Kanizsai, Anikó Pósa, Csaba Varga and László G. Puskás The Anti-Inflammatory Role of Mannich Curcuminoids; Special Focus on Colitis, Molecules, Special Issue: “Anti-Inflammatory Activity of Natural Products” 2019, 24(8), 1546

7. Gábor J. Szebeni, József A. Balog, András Demjén, Róbert Alföldi, Vanessza L. Végi, Liliána Z. Fehér, Imola Mán, Edit Kotogány, Barbara Gubán, Péter Batár, László Hackler Jr.,Iván Kanizsai and László G. Puskás Imidazo[1,2-b]pyrazole-7-carboxamides Induce Apoptosis in Human Leukemia Cells at Nanomolar Concentrations, Special Issue: "Pyrazole Derivatives” Molecules 2018, 23(11), 2845,

8. Anita K. Kovács, Péter Hegyes, Gábor J. Szebeni, Krisztián Bogár, László G. Puskás, Gábor K. Tóth Synthesis of N-Peptide-6-Amino-d-Luciferin Conjugates with Optimized Fragment Condensation Strategy, International Journal of Peptide Research and Therapeutics, 2018, doi.org/10.1007/s10989-018-9768-8,

9. András Demjén, Róbert Alföldi, Márió Gyuris, Anikó Angyal, László Hackler, Gábor J. Szebeni, János Wölfling, László G. Puskás, Iván Kanizsai, Synthesis, cytotoxic characterization and SAR study of imidazo[1,2-b]pyrazole-7-carboxamides, Archive der Pharmazie, 351:(7) Paper e1800062. 21 p. (2018)

10. Anita Kármen Kovács, Péter Hegyes, Gábor János Szebeni, Lajos István Nagy, László Géza Puskás, Gábor K. Tóth Synthesis of N-peptide-6-amino-D-luciferin Conjugates, Frontiers in Chemistry, 2018 Apr 19;6:120

Grants of the group from the last 5 years:

National Research, Development and Innovation Office GINOP-2.3.2-15-2016-00001

National Research, Development and Innovation Office GINOP-2.3.2-15-2016-00028

National Research, Development and Innovation Office GINOP-2.3.2-15-2016-00030

National Research, Development and Innovation Office GINOP-2.2.1-15-2017-00054

National Research, Development and Innovation Office 2018-1.3.1-VKE-2018-00018

National Research, Development and Innovation Office 2018-1.3.1-VKE-2018-00024

New Nat. Excellence Progr. of Human Capacities UNKP-19-4-SZTE-36

New Nat. Excellence Prog. of the Ministry for Innovation and Technology UNKP-18-4-SZTE-73

Janos Bolyai Research Scolarship of the Hungarian Academy of Sciences BO/00139/17/8