Our central research topic is the study of structure-function relationships in signaling enzymes, with a focus on protein tyrosine phosphatases. The aim is to contribute to the understanding of how their structural features are correlated with specific signaling functions. To this end, signaling enzymes are studied from several directions:
The combination of results thus obtained in this way is further used to shed light on the signaling mechanism and overall functional role of the given enzyme.
We have good experience and we are currently involved in the production, isolation and purification of recombinant proteins, expressed in both prokaryotic and eukaryotic systems. Our research activity is carried out through tools of molecular biology (recombinant DNA, site-directed mutagenesis, (RT)-PCR, Western blot, immunoprecipitation, etc.), spectroscopic analysis (UV-VIS and fluorescent spectrophotometry), cell biology, protein crystallization and enzyme kinetics.
Our ongoing research projects are:
External website: full link: https://www.nipne.ro/proiecte/pn3/20-projects.html
External website: full link: https://www.nipne.ro/proiecte/pn3/9-projects.html
External website: full link:
https://www.icbp.ro/static/en/en-networking_grants-grants-national_grants/pcca1contract_792012.html
External website: full link: https://www.nipne.ro/proiecte/pn2/149-projects.html
Current research directions:
(a) expression, purification and study of the mechanism of action of some proteins involved in synaptic transmission;
(b) creation of new conjugates based on afibodies with a potential therapeutic role in different forms of leukemia;
(c) biochemical study of tau protein acetylation with applicability in neurodegenerative diseases;
(d) study of signaling mechanisms involved in various cancer forms
RECENT PUBLICATIONS
1. |
„Synthesis and characterization of a novel [52Mn]Mn-labelled affibody based radiotracer for HER2+ targeting”: Balázs Váradi, Károly Brezovcsik, Zoltán Garda, Eniko Madarasi, Horea Szedlacsek, Rodica-Aura Badea, Andrei-Mihai Vasilescu, Adina-Gabriela Puiu, Aura Ionescu, Livia-Elena Sima, Cristian V.A. Munteanu, Simona Călăraș, Adrienn Vagner, Dezső Szikra, Ngô Minh Toàn, Tibor Nagy, Zoltán Szűcs, Stefan Eugen Szedlacsek, Gabor Nagy and Gyula Tircsó, Inorganic Chemistry Frontiers, Accepted:29 May 2023; First published: 06 Jun 2023; DOI https://doi.org/10.1039/D3QI00356F, |
2. |
„Designed Peptide Inhibitors of STEP Phosphatase-GluA2 AMPA Receptor Interaction Enhance the Cognitive Performance in Rats": Szedlacsek HS, Bajusz D, Badea RA, Pop A, Bică CC, Ravasz L, Mittli D, Mátyás D, Necula-Petrăreanu G, Munteanu CVA, Papp I, Juhász G, Hritcu L, Keserű GM, Szedlacsek-SE.; J Med Chem. 2022 Jan; https://pubmed.ncbi.nlm.nih.gov/34962802/ |
3. |
„Trojan horse treatment based on PEG-coated extracellular vesicles to deliver doxorubicin to melanoma in vitro and in vivo": Patras L, Ionescu AE, Munteanu C, Hajdu R, Kosa A, Porfire A, Licarete E, Rauca VF, Sesarman A, Luput L, Bulzu P, Chiroi P, Tranca RA, Meszaros MS, Negrea G, Barbu-Tudoran L, Potara M, Szedlacsek S, Banciu M; Cancer Biol Ther. 2021; https://pubmed.ncbi.nlm.nih.gov/34964693/ |
4. |
„Comparative Analysis Between Cellular Oncogenes and Viral Oncogenes”: Puiu, AG; Grigoras, O; Preda, MI; Constantin, M; Vasilescu, AM; Biointerface Research in Applied Chemistry; Review; Volume11; Issue3; Page 9939-9951; DOI10.33263/BRIAC113.99399951; Published JUN 15 2021; https://www.webofscience.com/wos/woscc/full-record/WOS:000591668100010. |
5. |
,,Regulation of TRPM8 Channel activity by Src-mediated Tyrosine Phosphorylation”: Alexandra Manolache, Tudor Selescu, G. Larisa Maier, Mihaela Mentel, Aura Elena Ionescu, Cristian Neacșu , Alexandru Babeș, Ștefan Eugen Szedlacsek. Journal of Cellular Physiology; 2020; https://pubmed.ncbi.nlm.nih.gov/31729029/ |
6. |
„Analysis of EYA3 phosphorylation by Src kinase identifies residues involved in cell Proliferation”: Aura E. Ionescu, Mihaela Mentel, Cristian V.A. Munteanu, Livia E. Sima, Eliza C. Martin, Georgiana Necula-Petrareanu; Ștefan E. Szedlacsek. International Journal of Molecular Sciences, Volume 20, Issue 24, 6307; 2019; https://pubmed.ncbi.nlm.nih.gov/31847183/ |
7. |
„Biological and molecular modifications induced by cadmium and arsenic during breast and prostate cancer development”: Environmental Research; Zimta, AA; Schitcu, V; Gurzau, E; Stavaru, C ; Manda, G; Szedlacsek, S; Berindan-Neagoe, Volume: 178, Article Number: 108700, DOI: 10.1016/j.envres; 2019; https://pubmed.ncbi.nlm.nih.gov/31520827/ |
8. |
„Crystal structure of a xylulose 5-phosphate phosphoketolase. Insights into the substrate specificity for xylulose 5-phosphate”: Journal of Structural Biology:Scheidig, AJ; Horvath, D; Szedlacsek, SE , Volume 207, Issue 1, Page 85-102; 2019; https://pubmed.ncbi.nlm.nih.gov/31059775/ |
9. |
„Collagen regulates the ability of endothelial progenitor cells to protect hypoxic myocardium through a mechanism involving miR-377/VE-PTP axis”: Rosca AM, Mitroi DN, Cismasiu V, Badea R, Necula-Petrareanu G, Preda MB, Niculite C, Tutuianu R, Szedlacsek S, Burlacu A. J Cell Mol Med. 22, 4700-4708; 2018; https://pubmed.ncbi.nlm.nih.gov/30044046/ |
10. |
„WDR1 is a novel EYA3 substrate and its dephosphorylation induces modifications of the cellular actin cytoskeleton”: Mentel M, Ionescu AE, Puscalau-Girtu I, Helm MS, Badea RA, Rizzoli SO, Szedlacsek SE. Sci Rep. 8, 2910; 2018; https://pubmed.ncbi.nlm.nih.gov/29440662/ |
11. |
„Phosphoketolases from Lactococcus lactis, Leuconostoc mesenteroides and Pseudomonas aeruginosa: dissimilar sequences, similar substrates but distinct enzymatic characteristics“, Petrareanu G, Balasu MC, Vacaru AM, Munteanu CV, Ionescu AE, Matei I, Szedlacsek SE.: Appl Microbiol Biotechnol. 98, 7855-67; 2014; https://pubmed.ncbi.nlm.nih.gov/24740691/ |
12. |
„Protein tyrosine phosphatase structure-function relationships in regulation and pathogenesis“: Böhmer F, Szedlacsek S, Tabernero L, Ostman A, den Hertog J., Febs J. 280, 413-31; 2013; https://pubmed.ncbi.nlm.nih.gov/22682070/ |
13. |
„Preliminary X-ray crystallographic analysis of the D-xylulose 5-phosphate phosphoketolase from Lactococcus lactis”: Petrareanu, G, Balasu, MC, Zander, U, Scheidig, AJ and Szedlacsek, S.E., Acta Cryst. F66, 805–807; 2010; https://pubmed.ncbi.nlm.nih.gov/20606278/ |
14. |
„Interface Analysis of the Complex between ERK2 and PTP-SL”: Balasu MC, Spiridon LN, Miron S, Craescu CT, Scheidig AJ, Petrescu AJ, Szedlacsek SE. PLoS One. 4(5), e5432; 2009; https://pubmed.ncbi.nlm.nih.gov/19424502/ |
15. |
„Analysis of Molecular Determinants of PRL-3”: Pascaru M, Tanase C, Vacaru AM, Boeti P, Neagu E, Popescu I, Szedlacsek SE., J Cell Mol Med. 13(9B), 3141-50; 2009; https://pubmed.ncbi.nlm.nih.gov/19040419/ |
16. |
„Protein tyrosine phosphatases, structure-function relationships”:Tabernero L, Aricescu AR, Jones EY, Szedlacsek SE; Febs J. 275, 867-82; 2008; https://pubmed.ncbi.nlm.nih.gov/18298793/ |
17 |
„Functional, fractal nonlinear response with application to rate processes with memory, allometry, and population genetics” : Vlad MO, Morán F, Popa VT, Szedlacsek SE, Ross J. Proc Natl Acad Sci USA., 104, 4798-803; 2007; https://pubmed.ncbi.nlm.nih.gov/17360340/ |
18 |
„Identification and specificity profiling of protein prenyltransferase inhibitors using new fluorescent phosphoisoprenoids”: Dursina B, Reents R, Delon C, Wu Y, Kulharia M, Thutewohl M, Veligodsky A, Kalinin A, Evstifeev V, Ciobanu D, Szedlacsek SE, Waldmann H, Goody RS, Alexandrov K; . J Am Chem Soc. 128, 2822-35; 2006; https://pubmed.ncbi.nlm.nih.gov/16506760/ |
19 |
„Fisher's theorems for multivariable, time- and space-dependent systems, with applications in population genetics and chemical kinetics”: Vlad MO, Szedlacsek SE, Pourmand N, Cavalli- Sforza LL, Oefner P, Ross J; Proc Natl Acad Sci USA. 102, 9848-53; 2005; https://pubmed.ncbi.nlm.nih.gov/15994224/
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The main idea of this project was that by inhibiting at least one of these two interactions of GluA2, the internalization of AMPAR will be reduced and therefore the synapse resistance will be increased, thus leading to improved cognitive functions.
The project is agreed as a bilateral collaboration between IBAR and ATOMKI, and the University of Debrecen and IFIN-HH participate in this project voluntarily.
The project is agreed as a joint collaboration among IBAR, ATOMKI and UD, the latter being a cost free participant. There are two main directions envisaged by the proposed project: - receptors mapping and therapy, using an affibody against HER2 receptors, combined with an adequate radioisotope. In this respect, the specific objectives are: a) expression and purification of affibodies; b) establishing labelling procedures; c) ex vivo and/or in vivo testing of optimal compounds.
Affibody molecules are highly promising therapeutic candidates due to their advantageous features like: small size, efficient delivery, straightforward engineering towards improved formats, site-directed conjugation of payloads, possibility of GMP production by chemical synthesis or inexpensive bacterial production leading to low product costs.
Project Funded under: Human resources and Mobility in the specific programme for research, technological development and demonstration "Structuring the European Research Area" under the Sixth Framework Programme 2002-2006. PTPNET is a training network for young scientists in the field of protein tyrosine phosphatase (PTP) research.
Proteins are essential players of all biological processes and they are involved in practically every function performed by a living cell.