Melanoma Biology
Head: Stjepan Uldrijan
Brno node
HOME INSTITUTION
Faculty of Medicine MU
RESEARCH PROGRAMME(S)
RP 1 - Molecular basis of cancer and molecular targets
RP 2 - Research and development of anticancer pharmaceuticals and therapeutic methods
Tumor cell resistance to targeted therapy is a problem that can be overcome.
- Mission: We want to understand the mechanisms enabling tumor cell growth and survival under stress conditions and the emergence of melanoma resistance to targeted treatment.
- Vision: We will find new targeted therapy options for melanoma patients whose tumors are resistant to BRAF and MEK kinase inhibitors.
Our research group studies molecular mechanisms responsible for cancer cell growth and survival under stress conditions, including their response to modern targeted therapies. We focus on the molecular biology of malignant melanoma, specifically on the mechanisms regulating the RAS/RAF/MEK/ERK signaling pathway, whose overactivation, induced by mutations in the NRAS and BRAF oncogenes, promotes aggressive melanoma growth. Clinically used inhibitors of BRAF and MEK kinases can significantly reduce the ERK pathway activity and thus slow melanoma progression, but patients often develop resistance to treatment. We aim for a more profound comprehension of the ERK pathway regulation and resistance development at the molecular level. This could help identify new and more effective targeted treatment options for this disease.
SELECTED PUBLICATIONS
- Štětková M, Growková K, Fojtík P, Valčíková B, Palušová V, Verlande A, Jorda R, Kryštof V, Hejret V, Alexiou P, Rotrekl V, Uldrijan S. CDK9 activity is critical for maintaining MDM4 overexpression in tumor cells. Cell Death Dis. 2020 Sep 15;11(9):754. DOI: 10.1038/s41419-020-02971-3
- Němec V, Hylsová M, Maier L, Flegel J, Sievers S, Ziegler S, Schröder M, Berger BT, Chaikuad A, Valčíková B, Uldrijan S, Drápela S, Souček K, Waldmann H, Knapp S, Paruch K. Furo[3,2-b]pyridine: A Privileged Scaffold for Highly Selective Kinase Inhibitors and Effective Modulators of the Hedgehog Pathway. Angew Chem Int Ed Engl. 2019 Jan 21;58(4):1062-1066. DOI: 10.1002/anie.201810312
- Verlande A, Krafčíková M, Potěšil D, Trantírek L, Zdráhal Z, Elkalaf M, Trnka J, Souček K, Rauch N, Rauch J, Kolch W, Uldrijan S. Metabolic stress regulates ERK activity by controlling KSR-RAF heterodimerization. EMBO Rep. 2018 Feb;19(2):320-336. DOI: 10.15252/embr.201744524
COLLABORATION WITHIN THE NICR
Jan Bouchal
(Olomouc node, Faculty of Medicine PU in Olomouc)
Lenka Bešše
(Brno node, Faculty of Medicine MU)
Pavel Krejčí
(Brno node, Faculty of Medicine MU)
Petr Beneš
(Brno node, Faculty of Science MU)
Vladimír Kryštof
(Olomouc node, Faculty of Medicine PU in Olomouc)
Zdeněk Andrysík
(Brno node, Faculty of Medicine MU)
SPECIALIZED EXPERTISE AND TECHNOLOGY
Malignant melanoma molecular biology
Regulation of ERK and AMPK signaling pathways
Tumor suppressor p53 regulation
A portfolio of advanced cell and molecular biology methods; 2D and 3D culture techniques under normoxia and hypoxia
Interactions of cancer and immune cells
Real-time analyses of cancer cell energy metabolism
COLLABORATION WITH LARGE RESEARCH INFRASTRUCTURES AND RESEARCH CENTRES
Central European Institute of Technology at Masaryk University CEITEC MU
National Infrastructure for Chemical Biology CZ-OPENSCREEN