CELL SIGNALING

We decipher cellular signals

Mgr. Pavel Krejčí, Ph.D.

E-mail: pavel.krejci@fnusa.cz

Key words

Morphogene Signaling, Receptor Tyrosine Kinases, Genetics of Bone Disorders, Primary Cilia, Fibroblast Growth Factor, Achondroplasia, Drug Development, Repurposing.

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 function in disease, 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, nature of effectors utilized by RTKs to regulate specific cell functions, mechanisms by which RTKs interact with primary cilia and morphogene signaling, and molecular pathologies of skeletal disorders caused by RTK mutations.

Main goals

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

Technological equipment

Confocal microscope, FPLC chromatography system.

Assistant

Milada Zajícová
E-mail: milada.zajicova@fnusa.cz

Team members

Mgr. Pavel Krejčí, Ph.D.
Milada Zajícová
Mgr. Michaela Bosáková, Ph.D.
Mgr. Bohumil Fafílek, Ph.D.
Mgr. Zuzana Feketová, Ph.D.
Mgr. Regina Gomolková
Ing. Martin Hrouzek
Ing. Jiří Šmíd, Ph.D.

Selected results

Kimura T, Bosakova M, Nonaka Y, Hruba E, Yasuda K, Futakawa S, Kubota T, Fafilek B, Gregor T, Abraham SP, Gomolkova R, Belaskova S, Pesl M, Csukasi F, Duran I, Fujiwara M, Kavkova M, Zikmund T, Kaiser J, Buchtova M, Krakow D, Nakamura Y, Ozono K, Krejci P. An RNA aptamer restores defective bone growth in FGFR3-related skeletal dysplasia in mice. Sci Transl Med. 2021 May 5;13(592):eaba4226.

Bosakova M, Abraham SP, Nita A, Hruba E, Buchtova M, Taylor SP, Duran I, Martin J, Svozilova K, Barta T, Varecha M, Balek L, Kohoutek J, Radaszkiewicz T, Pusapati GV, Bryja V, Rush ET, Thiffault I, Nickerson DA, Bamshad MJ; University of Washington Center for Mendelian Genomics, Rohatgi R, Cohn DH, Krakow D, Krejci P. Mutations in GRK2 cause Jeune syndrome by impairing Hedgehog and canonical Wnt signaling. EMBO Mol Med. 2020 Nov 6;12(11):e11739.

Kunova Bosakova M, Nita A, Gregor T, Varecha M, Gudernova I, Fafilek B, Barta T, Basheer N, Abraham SP, Balek L, Tomanova M, Fialova Kucerova J, Bosak J, Potesil D, Zieba J, Song J, Konik P, Park S, Duran I, Zdrahal Z, Smajs D, Jansen G, Fu Z, Ko HW, Hampl A, Trantirek L, Krakow D, Krejci P. Fibroblast growth factor receptor influences primary cilium length through an interaction with intestinal cell kinase. Proc Natl Acad Sci U S A. 2019 Mar 5;116(10):4316-4325.

Fafilek B, Balek L, Bosakova MK, Varecha M, Nita A, Gregor T, Gudernova I, Krenova J, Ghosh S, Piskacek M, Jonatova L, Cernohorsky NH, Zieba JT, Kostas M, Haugsten EM, Wesche J, Erneux C, Trantirek L, Krakow D, Krejci P. The inositol phosphatase SHIP2 enables sustained ERK activation downstream of FGF receptors by recruiting Src kinases. Sci Signal. 2018 Sep 18;11(548):eaap8608.

Balek L, Buchtova M, Kunova Bosakova M, Varecha M, Foldynova-Trantirkova S, Gudernova I, Vesela I, Havlik J, Neburkova J, Turner S, Krzyscik MA, Zakrzewska M, Klimaschewski L, Claus P, Trantirek L, Cigler P, Krejci P. Nanodiamonds as “artificial proteins”: Regulation of a cell signalling system using low nanomolar solutions of inorganic nanocrystals. Biomaterials. 2018 Sep;176:106-121.