Pavel Dráber

Laboratory of Biology of the Cytoskeleton

Centrosomes as anti-cancer targets.

Gliomas are the most common form of brain tumours with a poor prognosis. Despite the potential of a new generation of antimitotic drugs that bind to tubulin dimers, the success rate in treating the most aggressive types of gliomas (glioblastomas; GBM) is greatly reduced by the resistance that develops after the use of these agents. In addition, there are currently no clinically reliable methods that allow early identification of those gliomas that undergo malignant transformation. Alterations in centrosomal microtubule nucleation have been shown to influence the aggressive behaviour of tumour cells, and there are significant differences in the expression of proteins responsible for microtubule nucleation in GBMs compared with benign astrocytomas. In recent years, proteins that regulate the actin cytoskeleton and cell motility have also been shown to modulate microtubule nucleation. These regulatory proteins may therefore represent novel molecular targets for therapeutic strategies.

SELECTED PUBLICATIONS
  • Dráber P, Dráberová E. Dysregulation of Microtubule Nucleating Proteins in Cancer Cells. Cancers (Basel). 2021 Nov 11;13(22):5638. DOI: 10.3390/cancers13225638
  • Nejedlá M, Klebanovych A, Sulimenko V, Sulimenko T, Dráberová E, Dráber P, Karlsson R. The actin regulator profilin 1 is functionally associated with the mammalian centrosome. Life Sci Alliance. 2020 Nov 12;4(1):e202000655. DOI: 10.26508/lsa.202000655
  • Chafai DE, Sulimenko V, Havelka D, Kubínová L, Dráber P, Cifra M. Reversible and Irreversible Modulation of Tubulin Self-Assembly by Intense Nanosecond Pulsed Electric Fields. Adv Mater. 2019 Sep;31(39):e1903636. DOI: 10.1002/adma.201903636
  • Ivanova EL, Gilet JG, Sulimenko V, Duchon A, Rudolf G, Runge K, Collins SC, Asselin L, Broix L, Drouot N, Tilly P, Nusbaum P, Vincent A, Magnant W, Skory V, Birling MC, Pavlovic G, Godin JD, Yalcin B, Hérault Y, Dráber P, Chelly J, Hinckelmann MV. TUBG1 missense variants underlying cortical malformations disrupt neuronal locomotion and microtubule dynamics but not neurogenesis. Nat Commun. 2019 May 13;10(1):2129. DOI: 10.1038/s41467-019-10081-8
  • Dráberová E, D’Agostino L, Caracciolo V, Sládková V, Sulimenko T, Sulimenko V, Sobol M, Maounis NF, Tzelepis E, Mahera E, Křen L, Legido A, Giordano A, Mörk S, Hozák P, Dráber P, Katsetos CD. Overexpression and Nucleolar Localization of γ-Tubulin Small Complex Proteins GCP2 and GCP3 in Glioblastoma. J Neuropathol Exp Neurol. 2015 Jul;74(7):723-42. DOI: 10.1097/NEN.0000000000000212
SPECIALIZED EXPERTISE AND TECHNOLOGY

Microscopy of cytoskeletal structures

Analysis of microtubule nucleation and dynamics in cells

Isolation of tubulin, microtubules and centrosomes

 Monoclonal antibodies against cytoskeletal proteins

COLLABORATION WITH LARGE RESEARCH INFRASTRUCTURES AND RESEARCH CENTRES

National infrastructure for biological and biomedical imaging Czech-Bioimaging