A5070777703- Developmental Biology and Gene Regulation
- Epigenetics and DNA Methylation
- Pluripotent Stem Cells Research
- Animal Genetics and Reproduction
- Congenital heart defects research
- CRISPR and Genetic Engineering
- CAR-T cell therapy research
- Genomics and Chromatin Dynamics
- Prenatal Substance Exposure Effects
- Wnt/β-catenin signaling in development and cancer
- Renal and related cancers
- Plant Molecular Biology Research
- Cancer Immunotherapy and Biomarkers
- MicroRNA in disease regulation
- Neurogenesis and neuroplasticity mechanisms
- Hippo pathway signaling and YAP/TAZ
- Fish Ecology and Management Studies
- Cancer-related gene regulation
- Immunotherapy and Immune Responses
- Axon Guidance and Neuronal Signaling
- Circadian rhythm and melatonin
- RNA Research and Splicing
- Molecular Biology Techniques and Applications
- Planarian Biology and Electrostimulation
- Child Development and Digital Technology
University of Nottingham
2011-2023
Queen's Medical Centre
2014-2023
Adaptimmune (United Kingdom)
2016-2018
University of Dundee
2009-2010
Czech Academy of Sciences
2006-2009
Czech Academy of Sciences, Institute of Molecular Genetics
2006
Segmentation of the vertebrate body axis is initiated through somitogenesis, whereby epithelial somites bud off in pairs periodically from rostral end unsegmented presomitic mesoderm (PSM). The periodicity somitogenesis governed by a molecular oscillator that drives periodic waves clock gene expression caudo-rostrally PSM with matches somite formation. To date genes comprise components Notch, Wnt, and FGF pathways. literature contains controversial reports as to absolute role(s) Notch...
5-Methylcytosine (5mC) is an epigenetic modification involved in regulation of gene activity during differentiation. Tet dioxygenases oxidize 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). Both 5fC 5caC can be excised from DNA by thymine-DNA glycosylase (TDG) followed regeneration unmodified cytosine via the base excision repair pathway. Despite evidence that this mechanism operative embryonic stem cells, role TDG-dependent demethylation...
A common feature of development in most vertebrate models is the early segregation germ line from soma. For example, Xenopus and zebrafish embryos primordial cells (PGCs) are specified by plasm that inherited egg; mice, Blimp1 expression epiblast mediates commitment to line. How these disparate mechanisms PGC specification evolved unknown. Here, order identify ancestral mechanism vertebrates, we studied axolotl (Mexican salamander), a model for tetrapod ancestor. In axolotl, PGCs develop...
During somitogenesis, epithelial somites form from the pre-somitic mesoderm (PSM) in a periodic manner. This periodicity is regulated by molecular oscillator, known as 'segmentation clock', that characterised an oscillatory pattern of gene expression sweeps PSM caudal-rostral direction. Key components segmentation clock are intracellular Notch, Wnt and FGF pathways, it widely accepted negative-feedback loops regulate expression. However, open question field how oscillations coordinated,...
Patients with hepatocellular carcinoma (HCC) have a poor prognosis and limited therapeutic options. Alpha‐fetoprotein (AFP) is often expressed at high levels in HCC an established clinical biomarker of the disease. Expression AFP nonmalignant liver can occur, particularly subset progenitor cells during chronic inflammation, typically lower than HCC. This cancer‐specific overexpression indicates that may be promising target for immunotherapy. We verified expression normal diseased tissue...
Abstract Cell differentiation depends mainly on specific mRNA expression. To quantify the expression of a particular gene, normalisation with respect to reference gene is carried out. This based assumption that constant during development, in different cells or tissues after treatment. Xenopus laevis studies have frequently used eEF‐1 alpha, GAPDH, ODC, L8, and H4 as genes. The aim this work was examine, by real‐time RT‐PCR, profiles above‐mentioned five genes early development X. . It shown...
Somitogenesis is the earliest sign of segmentation in developing vertebrate embryo. This process starts very early, soon after gastrulation has initiated and proceeds an anterior-to-posterior direction during body axis elongation. It widely accepted that somitogenesis controlled by a molecular oscillator with same periodicity as somite formation. periodic mechanism repeated specific number times until embryo acquires defined specie-specific final somites at end varies between species. How...
Somites are formed progressively from the presomitic mesoderm (PSM) in a highly regulated process according to strict periodicity driven by an oscillatory mechanism. The Notch and Wnt pathways key components regulation of this somitic oscillator data Xenopus zebrafish embryos indicate that Notch-downstream target Nrarp participates both activities. We have analyzed Nrarp/nrarp-a expression PSM chick, mouse embryos, we show it cycles synchrony with other cyclic genes. In its transcription is...
5-Methylcytosine (5-mC) is an epigenetic modification associated with gene repression. Recent studies demonstrated that 5-mC can be enzymatically oxidised into 5-hydroxymethylcytosine and further 5-formylcytosine (5-fC) 5-carboxylcytsine (5-caC). 5-caC has been found in embryonic stem cells mouse pre-implantation embryos but no detectable levels of this have reported for somatic tissues to date. Whereas it suggested serve as intermediate the process active demethylation, function form...
Metazoans have multiple ETS paralogues with overlapping or indiscriminate biological functions. Elk-1, one of three mammalian ternary complex factors (TCFs), is a well-conserved, domain-containing transcriptional regulator mitogen-responsive genes that operates in concert serum response factor (SRF). Nonetheless, its genetic role remains unresolved because the elk-1 gene could be deleted from mouse genome seemingly without adverse effect. Here we explored evolution Elk-1 to gain insight into...
Pluripotency defines the unlimited potential of individual cells vertebrate embryos, from which all adult somatic and germ are derived. Understanding how programming pluripotency evolved has been obscured in part by a lack data lower vertebrates; model systems such as frogs zebrafish, function genes NANOG POU5F1 have diverged. Here, we investigated axolotl ortholog programs during development. Axolotl is absolutely required for gastrulation germ-layer commitment. We show that primitive...
Src family tyrosine kinases (SFKs) play important roles in cell morphology, differentiation, motility and proliferation. Elevated expression and/or specific activity of are characteristic for several types human cancer. However, little information is available about the role spatio-temporal SFKs early embryonic development. In this study we characterized, <i>Xenopus laevis</i>, patterns five SFK genes <i>src, fyn, yes, lyn</i> <i>laloo</i> as well <i>csk</i> gene, a negative regulator SFKs,...
Abstract The DNA methyl transferase inhibitors 5-aza-2’-deoxycytidine (decitabine or DECI) and 5-azacytidine (azacitidine AZA) have recently been approved for the treatment of a variety hematologic malignancies. These cytidine analogues remove repressive epigenetic marks induce transcription numerous genes normally silenced during processes cellular differentiation transformation. DNMTis net anti-neoplastic activity through up-regulation tumor-suppressor involved in induction apoptosis, cell...
Abstract Pluripotency defines the unlimited potential of cells in primitive ectoderm vertebrate embryos, from which all adult somatic and germ are derived. Understanding how programing pluripotency evolved has been obscured by study early development models lower vertebrates is not conserved. Here we investigated axolotl ortholog mammalian core factor NANOG , programs during to model tetrapod ancestor terrestrial evolved. We show that (animal caps; AC) synergizes with NODAL activity...