Group leader: Gergely Szakács, MD, PhD

Associated Group leader: András Füredi, PhD

 

The Laboratory of Organic anion transporting polypeptides (Principal Investigator: Csilla Laczka PhD DSc) and the Laboratory of Pathological Mineralisation (Principal Investigator: András Váradi PhD Dsc) are operate as independent units within the DRG.

 

General research interests

Anticancer therapies often become ineffective due to the emergence of multidrug resistance (MDR). Mechanisms ensuring survival of cancer cells include the inactivation or efflux of drug molecules, increased DNA repair, avoiding apoptosis, reducing target protein expression, suspending cell cycle, and bypassing immunosurveillance. Current estimations suggest that drug resistance and the resulting ineffectiveness of the drug treatment are responsible for up to 90% of the cancer related deaths.

The Drug Resistance Research Group is aiming to understand and target mechanisms of cancer drug resistance, by establishing new in vitro and in vivo models and by developing novel compounds and treatment strategies to target crucial cancer cell populations which drive relapse after therapy.

 

 

Projects

  • Identification and characterization of Multidrug resistant- or MDR-selective compounds
  • Development of LiPyDau, an extremely potent anticancer agent targeting therapy resistant tumors
  • Investigating the mechanisms of cisplatin resistance in triple negative breast cancer
  • Improving current chemotherapy protocols by personalization with algorithm-assisted therapy design
  • Developing a point-of-care microfluidic device for Therapeutic Drug Monitoring in cancer treatment
  • Studying the role of drug tolerant persisters in therapy resistance and relapse

 

Members

Group leader: Gergely Szakács, MD, PhD (https://m2.mtmt.hu/gui2/?type=authors&mode=browse&sel=10001932)

Associated Group leader: András Füredi, PhD (https://m2.mtmt.hu/gui2/?type=authors&mode=browse&sel=10032787)

Senior scientist: Éva Tusnády, PhD

Postdocs

Anna Lovrics, PhD (https://m2.mtmt.hu/gui2/?type=authors&mode=browse&sel=10047923)

Szilárd Tóth, PhD (https://m2.mtmt.hu/gui2/?type=authors&mode=browse&sel=10032964)

Nóra Varga, PhD (https://m2.mtmt.hu/gui2/?type=authors&mode=browse&sel=10047255)

PhD students

Eszter Bajtai (https://m2.mtmt.hu/gui2/?type=authors&mode=browse&sel=10072609) (shared supervision with József Tóvári, PhD, Dsc, National Institute of Oncology)

Dóra Bereczki (shared supervision with Péter Fürjes, PhD, HUN-REN Centre for Energy Research)

Balázs Gombos (https://m2.mtmt.hu/gui2/?type=authors&mode=browse&sel=10084115)

Lidia Ines Haffaressas

Flóra Vajda (https://m2.mtmt.hu/gui2/?type=authors&mode=browse&sel=10050548)

Assistant

Krisztina Dolniczki

Project manager

Krisztina Mohos

PhD degrees (from 2014)

Csilla Hegedüs (2014)

Viola Pomozi (2014)

Dóra Türk (2015)

Katalin Kiss (2015)

Koszarska Magdalena Renata (2015)

Krisztina Fülöp (2015)

András Füredi (2018)

Szilárd Tóth (2019)

Zsófia Rakvács (2020)

Izabel Patik (2020)

Lilla Hámori (2021)

Mihály Cserepes (2021)

Virág Székely (2021)

Tímea Windt (2022)

Laczkó-Rigó Réka (2022)

Kozák Eszter (2022)

 

Recent Publications

 

Szebényi*, A. Füredi*, E. Bajtai, S.N. Sama, A. Csiszar, B. Gombos, P. Szabó, M. Grusch, G. Szakács, Effective targeting of breast cancer by the inhibition of P-glycoprotein mediated removal of toxic lipid peroxidation byproducts from drug tolerant persister cells, Drug Resist. Updat. 71 (2023) 101007. https://doi.org/10.1016/j.drup.2023.101007.

L. Kovács, T. Ferenci, B. Gombos, A. Füredi, I. Rudas, G. Szakács, D.A. Drexler, Positive Impulsive Control of Tumor Therapy—A Cyber-Medical Approach, IEEE Trans. Syst. Man Cybern. Syst. (2023) 1–12. https://doi.org/10.1109/TSMC.2023.3315637.

Z. Gyöngy, G. Mocsár, É. Hegedűs, T. Stockner, Z. Ritter, L. Homolya, A. Schamberger, T.I. Orbán, J. Remenyik, G. Szakacs, K. Goda, Nucleotide binding is the critical regulator of ABCG2 conformational transitions, eLife 12 (2023) e83976. https://doi.org/10.7554/eLife.83976.

V.F.S. Pape, R. Palkó, S. Tóth, M.J. Szabó, J. Sessler, G. Dormán, É.A. Enyedy, T. Soós, I. Szatmári, G. Szakács, Structure–Activity Relationships of 8-Hydroxyquinoline-Derived Mannich Bases with Tertiary Amines Targeting Multidrug-Resistant Cancer, J. Med. Chem. 65 (2022) 7729–7745. https://doi.org/10.1021/acs.jmedchem.2c00076.

E. Karai, K. Szebényi, T. Windt, S. Fehér, E. Szendi, V. Dékay, P. Vajdovich, G. Szakács*, A. Füredi*, Celecoxib Prevents Doxorubicin-Induced Multidrug Resistance in Canine and Mouse Lymphoma Cell Lines, Cancers 12 (2020) 1117. https://doi.org/10.3390/cancers12051117.

M. Cserepes*, D. Türk*, S. Tóth, V.F.S. Pape, A. Gaál, M. Gera, J.E. Szabó, N. Kucsma, G. Várady, B.G. Vértessy, C. Streli, P.T. Szabó, J. Tovari, N. Szoboszlai, G. Szakács, Unshielding Multidrug Resistant Cancer through Selective Iron Depletion of P-Glycoprotein–Expressing Cells, Cancer Res. 80 (2020) 663–674. https://doi.org/10.1158/0008-5472.CAN-19-1407.

L. Hámori, G. Kudlik, K. Szebényi, N. Kucsma, B. Szeder, Á. Póti, F. Uher, G. Várady, D. Szüts, J. Tóvári, A. Füredi*, G. Szakács*, Establishment and Characterization of a Brca1/−, p53/− Mouse Mammary Tumor Cell Line, Int. J. Mol. Sci. 21 (2020) 1185. https://doi.org/10.3390/ijms21041185.

P. Kannan*, A. Füredi*, S. Dizdarevic, T. Wanek, S. Mairinger, J. Collins, T. Falls, R.M. van Dam, D. Maheshwari, J.T. Lee, G. Szakács, O. Langer, In vivo characterization of [18F]AVT-011 as a radiotracer for PET imaging of multidrug resistance, Eur. J. Nucl. Med. Mol. Imaging 47 (2020) 2026–2035. https://doi.org/10.1007/s00259-019-04589-w.

Z. Rakvács, N. Kucsma, M. Gera, B. Igriczi, K. Kiss, J. Barna, D. Kovács, T. Vellai, L. Bencs, J.M. Reisecker, N. Szoboszlai, G. Szakács, The human ABCB6 protein is the functional homologue of HMT-1 proteins mediating cadmium detoxification, Cell. Mol. Life Sci. (2019). https://doi.org/10.1007/s00018-019-03105-5.

T. Windt, S. Tóth, I. Patik, J. Sessler, N. Kucsma, Á. Szepesi, B. Zdrazil, C. Özvegy-Laczka, G. Szakács, Identification of anticancer OATP2B1 substrates by an in vitro triple-fluorescence-based cytotoxicity screen, Arch. Toxicol. 93 (2019) 953–964. https://doi.org/10.1007/s00204-019-02417-6.

*shared authorship

 

Collaborations

International

University of Bern, Bern (Switzerland)

Investigating drug resistance mechanisms in organoids and animal models

 

Medical University of Vienna, Vienna (Austria)

Developing novel treatments to eliminate drug tolerant persister cells

 

Seoul National University, Seoul (Korea)

University of Pennsylvania, Philadelphia (USA)

University of Freiburg, Freiburg (Germany)

 

National

Microsystem Laboratory, HUN-REN Centre for Energy Research, Budapest (Hungary):

Development of a point-of-care microfluidic device for Therapeutic Drug Monitoring in cancer treatment (POC-TDM), EU funded MSCA project (https://cordis.europa.eu/project/id/101065044)

 

Department of Experimental Pharmacology, National Institute of Oncology, Budapest (Hungary):

Modelling human cancer in mice, in vivo testing of new drug candidates

 

Óbuda University, Budapest (Hungary):

Chemotherapy individualization using algorithm-assisted therapy design

 

University of Szeged, Szeged (Hungary):

Characterization of metal-8-hydroxyquinoline complexes

 

University of Pécs, Pécs (Hungary):

Development of a novel bioimpedance-based diagnostic tool for early cancer detection

 

Eötvös Lóránd University, Budapest (Hungary):

Ongoing patent application for an extremely effective liposomal anticancer agent, Monitoring metal ions in cancer cells

 

Budapest University of Technology and Economics, Budapest (Hungary):

Testing anticancer cinchona alkaloids

 

R&D Companies

Actome GmbH, Freiburg (Germany)

Investigating of protein-protein and protein-lncRNA interactions in cellular senescence

 

Clinomics Europe Ltd, Budapest (Hungary)

Identifying circulating tumor cells in blood samples

 

Creative Cell Ltd., Budapest (Hungary)

Testing radioprotective agents on human cell lines

 

Collaborations within the Research Centre for Natural Sciences:

Epigenetic and Genome Editing Research Group, Institute of Molecular Life Sciences

Genome Stability Research Group, Institute of Molecular Life Sciences

Metabolic Drug-interactions Research Group, Institute of Molecular Life Sciences

Non-coding Genome Research Group, Institute of Molecular Life Sciences

Chemical Biology Research Group, Institute of Organic Chemistry

Medicinal Chemistry Research Group, Institute of Organic Chemistry

Functional Nanoparticles Research Group, Institute of Materials and Environmental Chemistry

Biological Nanochemistry Research Group, Institute of Materials and Environmental Chemistry

Centre for Structural Science

Brain Imaging Centre

 

 

Leader

Gergely Szakács

Members