Research focus

Maintenance of tissue homeostasis depends on extracellular signals that govern basic cell functions. Receptor tyrosine kinases (RTKs) represent major molecular tools of such cell-to-cell communications. RTK importance is further emphasised by evidence of their pathological functions, with more than 80 human pathologies associating with alterations in RTK genes, including cancer, developmental disorders and metabolic syndromes. Our research focuses on several poorly known areas of RTK function, such as the composition of protein complexes associating with activated RTKs at the cell membrane, the nature of effectors utilized by RTKs to regulate specific cell functions, the mechanisms by which RTKs interact with primary cilia and morphogene signaling, and the molecular pathologies of skeletal disorders caused by RTK mutations.

Research objectives

  • Unravel the mechanism of primary cilia regulation by RTKs.
  • Determine the extent of transactivation among the human RTKs.
  • Develop new treatments for FGFR3-related chondrodysplasias.

Top publications

  • GUDERNOVA, I., FOLDYNOVA-TRANTIRKOVA, S., EL GHANNAMOVA, B., FAFILEK, B., VARECHA, M., BALEK, L., HRUBA, E., JONATOVA, L., JELINKOVA, I., BOSAKOVA, M., TRANTIREK, L., MAYER, J., KREJCI, P. One reporter for in-cell activity profiling of majority of protein kinase oncogenes. eLife. 2017, 6, e21536.
  • TAYLOR, S., KUNOVA BOSAKOVA, M., VARECHA, M., BALEK, L., BARTA, T., TRANTIREK, L., JELINKOVA, I., DURAN, I., VESELA, I., FORLENZA, K., MARTIN, J., HAMPL, A., BAMSHAD, M., NICKERSON, D., JAWORSKI, M., SONG, J., WAN KO, H., COHN, D., KRAKOW, D., KREJCI, P. An inactivating mutation in intestinal cell kinase, ICK, impairs hedgehog signalling and causes short rib-polydactyly syndrome. Human Molecular Genetics. 2016, 25, 3998-4011.
  • MERRILL AE., SARUKHANOV A., KREJCI P., IDONI B., CAMACHO N., ESTRADA KD., LYONS KM., DEIXLER H., ROBINSON H., CHITAYAT D., CURRY CJ., LACHMAN RS., WILCOX WR., KRAKOW D. Bent bone dysplasia-FGFR2 type, a distinct skeletal disorder, has deficient canonical FGF signaling. American Journal of Human Genetics. 2012, 90, 550-7.
  • WANG Y., ZHOU X., OBEROI K., PHELPS R., COUWENHOVEN R., SUN M., REZZA A., HOLMES G., PERCIVAL CJ., FRIEDENTHAL J., KREJCI P., RICHTSMEIER JT., HUSO DL., RENDL M., JABS EW. p38 Inhibition ameliorates skin and skull abnormalities in Fgfr Beare-Stevenson mice. Journal of Clinical Investigation. 2012, 122, 2153-64.
  • SCUTO A., KREJCI P., POPPLEWELL L., WU J., WANG Y., KUJAWSKI M., KOWOLIK C., XIN H., CHEN L., WANG Y., KRETZNER L., YU H., WILCOX WR., YEN Y., ROMAN S., JOVE R. The novel JAK inhibitor AZD1480 blocks STAT3 and FGFR3 signaling, resulting in suppression of human myeloma cell growth and survival. Leukemia. 2011, 25, 538-50.

Other selected results

  • Development of novel reporter tools for in-cell RTK activity profiling.
  • Unraveling the mechanism of lethal ciliopathy caused by mutation in ICK kinase.
  • Elucidation of mechanism of action of FGF tyrosine kinase inhibitors in skeletal dysplasia.
  • Description of a novel human genetic condition, Bent Bone Dysplasia-FGFR2 type, caused by defective FGFR2 signaling.
  • Characterization of a novel inhibitor of FGFR and JAK kinases in multiple myeloma.

Team members

  • Mgr. Pavel Krejčí, Ph.D.
  • Mgr. Michaela Bosáková, Ph.D.
  • Mgr. Bohumil Fafílek, Ph.D.
  • Mgr. Tomáš Gregor
  • Ing. Monika Siekelová
  • Ing. Michaela Stroblová, Ph.D.
  • Marie Tesařová, Ph.D.
  • MUDr. Jan Ulbrych

Principal Investigator

Mgr. Pavel Krejčí, Ph.D.
Mgr. Pavel Krejčí, Ph.D.
Principal Investigator