A5055411966- Hemoglobinopathies and Related Disorders
- Iron Metabolism and Disorders
- Prenatal Screening and Diagnostics
- Epigenetics and DNA Methylation
- Erythrocyte Function and Pathophysiology
- Trace Elements in Health
- Cystic Fibrosis Research Advances
- Immunodeficiency and Autoimmune Disorders
- Neonatal Health and Biochemistry
- Chronic Myeloid Leukemia Treatments
- Virus-based gene therapy research
- Animal Genetics and Reproduction
- Kruppel-like factors research
- Pancreatic function and diabetes
- CRISPR and Genetic Engineering
- Blood groups and transfusion
- Synthesis and biological activity
- Genetics, Bioinformatics, and Biomedical Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- S100 Proteins and Annexins
- Protease and Inhibitor Mechanisms
- Fungal Plant Pathogen Control
- PARP inhibition in cancer therapy
- bioluminescence and chemiluminescence research
- Cancer-related gene regulation
Cyprus Institute of Neurology and Genetics
2009-2020
Freie Universität Berlin
2017
John Radcliffe Hospital
2002-2009
University of Oxford
2002-2009
University College London
1997-2000
Abstract Haemoglobinopathies are the most common monogenic diseases, posing a major public health challenge worldwide. Cyprus has one highest prevalences of thalassaemia in world and been first country to introduce successful population-wide prevention programme, based on premarital screening. In this study, we report significant comprehensive update status haemoglobinopathies for at least two decades. First, identified analysed all known 592 β-thalassaemia patients 595 Hb H disease Cyprus....
Aim: In humans, fetal hemoglobin (HbF) production is controlled by many intricate mechanisms that, to date, remain only partly understood. Patients & methods: Pharmacogenomic analysis of the effects hydroxyurea (HU) on HbF was undertaken in a collection Hellenic βthalassemia and sickle cell disease (SCD) compound heterozygotes healthy KLF1-haploinsufficient Maltese adults, identify genomic signatures that follow high patterns. Results: KLF10 emerged as top candidate. Moreover, genotype major...
The CFTR (cystic fibrosis transmembrane conductance regulator) gene shows a complex pattern of expression with tissue-specific and temporal regulation. However, the genetic elements transcription factors that control are largely unidentified. promoter does not confer tissue specificity on expression, suggesting there regulatory outside upstream region. Analysis potential defined as DNase 1-hypersensitive sites within introns revealed multiple predicted binding for HNF1alpha (hepatocyte...
B-thalassaemia and sickle cell disease (SCD) are two of the most common monogenic diseases that found in many populations worldwide. In both disorders clinical severity is highly variable, with persistence fetal haemoglobin (HbF) being one major ameliorating factors. HbF levels affected by, amongst other factors, single nucleotide polymorphisms (SNPs) at BCL11A gene HBS1L-MYB intergenic region, which located outside β-globin locus. For this reason, we developed multiplex assays allow...
The cystic fibrosis transmembrane conductance regulator ( CFTR ) gene shows a complex pattern of expression, with temporal and spatial regulation that is not accounted for by elements in the promoter. One approach to identifying regulatory mapping DNase I hypersensitive sites (DHS) within locus. We previously identified at least 12 clusters DHS across here further evaluate introns 2, 3, 10, 16, 17a, 18, 20 21 assess their functional importance expression. Transient transfections enhan‐...
To help clarify the hematological picture of patients who may be positive for β- and δ-globin gene mutations, following study was carried out. Our aim to identify mutations found in Greek Cypriot population, their frequencies Hb A2 values associated with them. Seventy-four samples were selected from a random sample 5,030 individuals, database Molecular Genetics Thalassaemia Department containing diagnostic analyses data also mined relevant information.Four novel Cyprus mutations: −30 (T→C),...
The first epidemiological study for thalassemia in Cyprus was performed by Fawdry 1946. determined that the frequency of β-thalassemia (β-thal) carriers around 18.0% and α0-thal (individuals with both cis α-globin genes inactive) at 2.0%. In 1998, another concluded had one highest frequencies β-thal worldwide (17.2%). Based on Haldane's hypothesis malaria might be selective agent responsible maintenance high levels sickle cell disease many populations world, it is expected following...
Cyprus, located at the eastern end of Mediterranean region, has been a place and western civilizations, presence various hemoglobin (Hb) variants can be considered testimony to past colonizations island. In this study, we report structural Hb identified in Cypriot population (Greek Cypriots, Maronites, Armenians, Latinos) during thalassemia screening 248,000 subjects carried out Thalassaemia Centre, Nicosia, over period 26 years. A sample 65,668 people was used determine frequency...
We describe the identification of a novel missense mutation in second zinc finger KLF1 two siblings who, based on their genotype, are predicted to suffer from beta thalassemia major but are, fact, transfusion-free and good health. These individuals, as well additional members same family also carrying this mutation, exhibit high levels fetal hemoglobin (HbF). is an erythroid transcription factor, which plays critical role regulation developmental switch between adult by regulating expression...
We report two cases of compound heterozygote patients for the --(MED I) and Hb Agrinio [alpha29(B10)Le-->uPro (alpha2)] anomalies in unrelated Greek Cypriot families. The first patient had a serious form H disease died at age 21 due to complications arising during an operation. second showed severe hematological picture has been regularly transfused since early age. This exhibits bone abnormalities as well hepatosplenomegaly. severity these incidences emphasizes need inclusion screening test...
Nondeletional hereditary persistence of fetal hemoglobin (nd-HPFH), a rare condition resulting in elevated levels (Hb F) adults, is associated with promoter mutations the human globin (HBG1 and HBG2) genes. In this paper, we report novel type nd-HPFH due to HBG2 gene mutation (HBG2:g.-109G>T). This mutation, located at 3' end distal CCAAT box, was initially identified an adult female subject Central Greek origin results Hb F (4.1%) significantly increased Ggamma-globin chain production...
β-Thalassemia (β-thal) is a hemoglobinopathy characterized by reduced or absent β-globin production. Pharmacological reactivation of the γ-globin gene for production fetal hemoglobin (Hb F) presents an attractive treatment strategy. In effort to identify promising therapeutic agents, we evaluated 80 analogues histone deacetylase inhibitor MS-275, known Hb F inducer. The chemical were identified via molecular modeling and targeted modifications. Nine novel agents exhibited significant...
Reactivation of γ-globin is considered a promising approach for the treatment β-thalassemia and sickle cell disease. Therapeutic induction expression, however, fraught with lack suitable therapeutic targets. The aim this study was to investigate effects that decitabine has on proteome human primary erythroid cells from healthy thalassemic volunteers, as means identifying new potential pharmacological Decitabine known inducer, which not, safe enough clinical use. A proteomic utilizing...
Thalassemias are the most common monogenic gene disorders in world. Patients present with a wide variability of clinical phenotypes ranging from severe phenotype (β-thalassemia major) to very mild, almost symptomless, condition. This is owing presence large number genetic modifiers affecting disease. treated blood transfusions and iron chelation therapy. Pharmacological therapies have varying degrees success depending on disease patients. Studies undertaken identify all that affect...