A5060900793- Heart Rate Variability and Autonomic Control
- Genomic variations and chromosomal abnormalities
- Cardiovascular and exercise physiology
- Chromosomal and Genetic Variations
- Microtubule and mitosis dynamics
- Cancer Genomics and Diagnostics
- Genomics and Rare Diseases
- Infrared Thermography in Medicine
- Cancer-related Molecular Pathways
- Cell Adhesion Molecules Research
- Genomics and Chromatin Dynamics
- Prenatal Screening and Diagnostics
- Congenital heart defects research
- DNA Repair Mechanisms
- Genetic Syndromes and Imprinting
- Cystic Fibrosis Research Advances
- Ovarian cancer diagnosis and treatment
- Epigenetics and DNA Methylation
- Neonatal Respiratory Health Research
- Spaceflight effects on biology
- Nutrition and Health Studies
- MicroRNA in disease regulation
- High Altitude and Hypoxia
- Cardiovascular Syncope and Autonomic Disorders
- Thermoregulation and physiological responses
Charles University
2012-2021
Ontario Institute for Cancer Research
2006-2011
Queen's University
2010
Princess Margaret Cancer Centre
2006-2009
University of Toronto
2009
Mount Sinai Hospital
2009
University Health Network
2008
Masaryk University
2006
Agilent Technologies (United States)
2006
Aneuploidy is a characteristic feature of established cancers and can promote tumor development. may arise directly, through unequal distribution chromosomes into daughter cells, or indirectly, tetraploid intermediate. The polo family kinase Plk4/Sak required for late mitotic progression haploinsufficient suppression in mice. Here we show that loss heterozygosity (LOH) occurs at the Plk4 locus 50% human hepatocellular carcinomas (HCC) present even preneoplastic cirrhotic liver nodules. LOH...
Some cancers have been stratified into subclasses based on their unique involvement of specific signaling pathways. The mapping human cancer genomes is revealing a vast number somatic alterations; however, the identification clinically relevant molecular tumor and respective driver genes presents challenges. This information key to developing more targeted personalized therapies. Here, we generate new mouse model genomically unstable osteosarcoma (OSA) that phenocopies disease. Integrative...
Pif1 is a 5-to-3 DNA helicase critical to replication and telomere length maintenance in the budding yeast Saccharomyces cerevisiae.ScPif1 negative regulator of telomeric repeat synthesis by telomerase, recombinant ScPif1 promotes dissociation telomerase RNA template from vitro.In order dissect role mPif1 mammals, we cloned disrupted gene.In wild-type animals, expression was detected only embryonic hematopoietic lineages.mPif1 ؊/؊ mice were viable at expected frequencies, displayed no...
Sporadic ovarian cancer is a particularly aggressive tumor characterized by highly abnormal karyotypes exhibiting many features of genomic instability. More complex changes in tumors arise as consequence chromosomal instability (CIN), which can generate both numerical [(N)-CIN] and structural [(S)-CIN]. In this study, molecular cytogenetic analysis was used to evaluate the relative levels (N)-CIN (S)-CIN. Six had near-diploid chromosome number, two were near-tetraploid, near-triploid....
Hypertension, which is a common cardiovascular disease in adults, could originate childhood. The aim of the study was to show differences baroreflex sensitivity and short-term blood-pressure variability between healthy hypertensive children, adolescents young those with white-coat effect respect obesity. We examined 54 subjects (11-21 years) who had repeatedly high causal blood pressure. Basing on 24-hour pressure monitoring, were divided into groups: 24 hypertension (Hy) 30 (WhC). Hy WhC...
Kabuki syndrome (KS) is a dominantly inherited disorder mainly due to de novo pathogenic variation in KMT2D or KDM6A genes. Initially, representative cohort of 14 Czech cases with clinical features suggestive KS was analyzed by experienced geneticists collaboration other specialties, and observed disease were evaluated according the 'MLL2-Kabuki score' defined Makrythanasis et al. Subsequently, aforementioned genes Sanger sequenced copy number analysis performed MLPA, followed genome-wide...
Abstract We report the clinical findings of 26 individuals from 16 unrelated families carrying variants in COL2A1 or COL11A1 genes. Using Sanger and next‐generation sequencing, 11 different (seven novel), were identified 13 (19 affected individuals), all diagnosed with Stickler syndrome (STL) type 1. In nine families, disease‐causing variant arose de novo. Phenotypically, we observed myopia (95%) retinal detachment (47%), joint hyperflexibility (92%), midface retrusion (84%), cleft palate...
Abstract Array comparative genomic hybridization (aCGH) is a key platform to assess cancer profiles. Many structural aberrations cannot be detected by aCGH alone. We have applied molecular cytogenetic analyses including spectral karyotyping, multicolor banding, and fluorescence in situ with comprehensively investigate the associated cisplatin resistance A2780 ovarian cells. well‐established model of chemotherapeutic distinct karyotypic abnormalities parental cisplatin‐resistant Cytogenetic...
The distal end of mouse chromosome 7 (Chr 7) contains a large cluster imprinted genes. In this region two cis-acting imprinting centers, IC1 (H19 DMR) and IC2 (KvDMR1), define proximal subdomains, respectively. To assess the functional independence in context Chr 7, we developed recombinase-mediated truncation strategy embryonic stem cells generated terminal deletion allele, DelTel7, with breakpoint between subdomains. We obtained germ line transmission truncated viable paternal...
Imprinted genes are commonly clustered in domains across the mammalian genome, suggesting a degree of coregulation via long-range coordination their monoallelic transcription. The distal end mouse chromosome 7 (Chr 7) contains two clusters imprinted within ∼1 Mb domain. This region is conserved on human 11p15.5 where it implicated Beckwith–Wiedemann syndrome. In both species, regulation requires critical cis-acting imprinting centres, carrying different germline epigenetic marks and...
Amplification of oncogenes and closely linked flanking genes is common in some types cancer can be associated with complex chromosome rearrangements and/or co-amplification non-syntenic chromosomal regions. To better understand the etiology structural complexity focal <i>MYCN</i> amplicons human neuronal cancer, we investigated precise locations high copy number genomic regions amplified cell lines. An integrated cytogenetic map amplicon was created using high-resolution array...
11100 Background: The pathogenesis of hepatocellular carcinoma (HCC) is multifactorial and includes genetic predisposition, though the precise nature latter as yet poorly understood. Mice heterozygous for polo like kinase Plk4 develop spontaneous HCC human cases show a high rate LOH (loss heterozygosity) at locus. We hypothesize that haploinsufficient tumor suppressor in man. purpose this study was to investigate mechanisms by which 50% reduction leads carcinogenesis. Methods: established ±...