A5013292411- Fibroblast Growth Factor Research
- Epigenetics and DNA Methylation
- Connective tissue disorders research
- Cancer-related gene regulation
- Wnt/β-catenin signaling in development and cancer
- PI3K/AKT/mTOR signaling in cancer
- Immune Response and Inflammation
- Bone fractures and treatments
- NF-κB Signaling Pathways
- Chronic Myeloid Leukemia Treatments
- Digestive system and related health
- RNA modifications and cancer
- Viral Infectious Diseases and Gene Expression in Insects
- Neurobiology and Insect Physiology Research
- Fungal Plant Pathogen Control
- Proteoglycans and glycosaminoglycans research
- Virus-based gene therapy research
- Protein Kinase Regulation and GTPase Signaling
- bioluminescence and chemiluminescence research
- Cytokine Signaling Pathways and Interactions
- Genetic factors in colorectal cancer
- Gene Regulatory Network Analysis
- Cancer Research and Treatments
- Neonatal Respiratory Health Research
- Macrophage Migration Inhibitory Factor
Masaryk University
2017-2025
St. Anne's University Hospital Brno
2017-2025
University Hospital Brno
2017-2025
Czech Academy of Sciences, Institute of Animal Physiology and Genetics
2019-2024
Institute of Animal Physiology of the Slovak Academy of Sciences
2023-2024
Johns Hopkins University
2023
Institute of Nanotechnology
2023
Goethe Institut
2023
Goethe University Frankfurt
2023
Czech Academy of Sciences
2009-2016
The differential signaling of multiple FGF ligands through a single fibroblast growth factor (FGF) receptor (FGFR) plays an important role in embryonic development. Here, we use quantitative biophysical tools to uncover the mechanism behind differences FGFR1c response FGF4, FGF8, and FGF9, process which is relevant for limb bud outgrowth. We find that FGF8 preferentially induces FRS2 phosphorylation extracellular matrix loss, while FGF4 FGF9 induce cell arrest. Thus, demonstrate biased...
We report reversal of the FGFR3-related skeletal dysplasia by RNA aptamer designed to neutralize FGFR3 ligand FGF2.
Most of our knowledge protein structure and function originates from experiments performed with purified proteins resuspended in dilute, buffered solutions. However, most crowded intracellular environments complex compositions. Significant efforts have been made to develop tools study their native cellular settings. Among these tools, in-cell NMR spectroscopy has the sole technique for characterizing space living cells at atomic resolution physiological temperature. Nevertheless, due...
The scaffold function of the inositol phosphatase SHIP2 mediates sustained ERK signaling downstream FGF receptors.
Significance A properly functioning primary cilium is prerequisite for both normal development and aging of all ciliated organisms, including humans. In vertebrates, the signaling Hedgehog family morphogens depends entirely on cilium. Recently, we reported that fibroblast growth factors (FGF) interacts with Hedgehog, this a consequence FGF regulating length speed processes happen therein. report, provide molecular mechanism such interaction, identifying intestinal cell kinase as mediator...
A major outcome of the canonical Wnt/β-catenin-signalling pathway is transcriptional activation a specific set target genes. typical feature response induced by Wnt signalling involvement Tcf/Lef factors that function in nucleus as principal mediators signalling. Vertebrate proteins perform two well-characterized functions: association with β-catenin they activate gene expression, and absence ligands bind TLE/Groucho to act repressors. Although general characteristics are well understood,...
Hypermethylated in cancer 1 (HIC1) represents a prototypic tumor suppressor gene frequently inactivated by DNA methylation many types of solid tumors. The encodes sequence-specific transcriptional repressor controlling expression several genes involved cell cycle or stress control. In this study, Hic1 allele was conditionally deleted, using Cre/loxP system, to identify influenced the loss Hic1. One transcripts upregulated upon ablation is toll-like receptor 2 (TLR2). Tlr2 levels increased...
ABSTRACT Osteogenesis imperfecta (OI) is a genetically heterogenous disorder most often due to heterozygosity for mutations in the type I procollagen genes, COL1A1 or COL1A2. The characterized by bone fragility leading increased fracture incidence and long-bone deformities. Although multiple mechanisms underlie OI, endoplasmic reticulum (ER) stress as cellular response defective collagen trafficking emerging contributor OI pathogenesis. Herein, we used 4-phenylbutiric acid (4-PBA), an...
The activity of the Wnt pathway undergoes complex regulation to ensure proper functioning this principal signaling mechanism during development adult tissues. may occur at several levels and includes both positive negative feedback loops. In present study we employed one such regulators, naked cuticle homolog 1 (Nkd1), follow in intestine liver neoplasia originated these organs. Using lineage tracing transgenic mice localized Nkd1 mRNA bottom parts small intestinal crypts hepatocytes...
In-cell profiling enables the evaluation of receptor tyrosine activity in a complex environment regulatory networks that affect signal initiation, propagation and feedback. We used FGF-receptor signaling to identify EGR1 as locus strongly responds activation majority recognized protein kinase oncogenes, including 30 kinases 154 their disease-associated mutants. The promoter was engineered enhance trans-activation capacity optimized for simple screening assays with luciferase or fluorescent...
HIC1 (hypermethylated in cancer 1) is a tumor suppressor gene located on chromosome 17p13.3, region frequently hypermethylated or deleted human neoplasias. In mouse, Hic1 essential for embryonic development and exerts an antitumor role adult animals. Since Hic1-deficient mice die perinatally, we generated conditional null allele by flanking the Hic1-coding loxP sites. When crossed to animals expressing Cre recombinase cell-specific manner, will provide new insights into function of...
In-cell NMR spectroscopy is the sole technique for characterizing protein structure, dynamics, and interactions in living human cells at atomic resolution. However, its applications have been restricted to asynchronous single-cell suspensions. We developed a strategy based on target inducible overexpression stably transfected cells, allowing acquisition of high-resolution in-cell spectra physiologically defined cellular states 3D tissue models.
Activin receptor-like kinases 1-7 (ALK1-7) regulate a complex network of SMAD-independent as well SMAD-dependent signaling pathways. One the widely used inhibitors for functional investigations these processes, in particular bone morphogenetic protein (BMP) signaling, is
The Wnt pathway plays a crucial role in self-renewal and differentiation of cells the adult gut. In present study, we revealed functional consequences inhibition canonical signaling intestinal epithelium. study was based on generation novel transgenic mouse strain enabling inducible expression an N-terminally truncated variant nuclear effector T cell factor 4 (TCF4). TCF4 acting as dominant negative (dn) version wild-type (wt) protein decreased transcription β-catenin-TCF4-responsive genes....
The differential signaling of multiple FGF ligands through a single fibroblast growth factor (FGF) receptor (FGFR) plays an important role in embryonic development. Here, we use quantitative biophysical tools to uncover the mechanism behind differences FGFR1c response FGF4, FGF8, and FGF9, process which is relevant for limb bud outgrowth. We find that FGF8 preferentially induces FRS2 phosphorylation extracellular matrix loss, while FGF4 FGF9 induce cell arrest. Thus, demonstrate biased...
Abstract Achondroplasia is the most common form of human dwarfism caused by mutations in FGFR3 receptor tyrosine kinase. Current therapy begins at two years age and improves longitudinal growth but does not address cranial malformations including midface hypoplasia foramen magnum stenosis, which lead to significant otolaryngeal neurologic compromise. A recent clinical trial found partial restoration defects with starting 3 months age, results are still inconclusive. The benefits...
Many tyrosine kinase inhibitors (TKIs) have failed to reach human use due insufficient activity in clinical trials. However, the TKIs may still benefit patients if their other targets are identified by providing treatment focused on syndromes driven these kinases. Here, we searched for novel of AZD1480, an inhibitor JAK2 that recently phase two cancer trials a lack activity. Twenty seven receptor kinases (RTKs) and 153 disease-associated mutants were in-cell profiled presence AZD1480 using...