Molecular Genetics Thalassaemia Department

Research

Research activities include the chemical reactivation of fetal haemoglobin for the therapy of β-thalassaemia, development of methods for the non-invasive prenatal diagnosis (NIPD) of β-thalassaemia, pharmacogenomic analysis of β-thalassaemia patients under hydroxyurea treatment, advancing and customising gene therapy for β-thalassaemia, and the ITHANET portal as a community portal for thalassaemias and haemoglobinopathies.

Service-related research programs

Epidemiological studies

•   Studies on the molecular basis of different forms of thalassaemia in Cyprus and other neighbouring countries
•   Determination of the frequencies and geographic distribution of the different forms of thalassaemia

Case studies and patient-group studies

•   Identification of patients and disease carriers of novel mutations and haemoglobin variants. Characterization of pertaining novel mutations and variants and of disease modifiers for thalassaemia and related studies.
•   Standardization of simple methods for the identification of thalassaemia mutations

Genotype/phenotype correlation studies in thalassaemia [ThaPheGe, funding]

•   Genotype/phenotype correlation studies in patients with β-thalassaemia and determination of the genetic factors responsible for ameliorating the clinical condition of the disease
•   Genotype/phenotype correlation studies in HbH disease patients
•   Genotype/phenotype correlation studies in carriers of thalassaemia traits

Drug therapy for thalassaemia

The aim of the project is to find compounds that increase the level of foetal haemoglobin and can be used for thalassaemia treatment.
•   A large number of compounds are examined and their effect on the level of foetal haemoglobin is determined. Additionally, new medicinal products are engineered based on promising lead compounds.
•   The effect of a number of drugs on the reactivation of foetal haemoglobin is examined. Pertaining animal models and patient-derived haematopoietic cells receive each drug and are examined for critical disease parameters after differentiation in vitro (FBC, globin levels HbF, F cells, mRNA and others).

Gene therapy for thalassaemia

Gene-therapeutic intervention promises the permanent cure of thalassaemia, and our group is developing a series of innovative tools designed to provide
• generally enhanced treatment efficacy compared to standard gene-therapy vectors
• specific activity for β-thalassaemia mutations common in Cyprus
Our current work is based on a well-characterised, efficient and safe lentiviral vector system combined with shRNA technology and draws on murine model systems and human primary cells for analysis of safety and efficacy.

Development of pre-implantation genetic diagnosis (PGD) for inherited disorders

PGD analyses are critical for the control of inherited disorders e.g. where couples of carriers for the same recessive disease choose to conceive a child.

Non-invasive prenatal diagnosis (NIPD) for thalassaemia

The aim of the project is to determine whether the analysis of cell-free foetal DNA detected in the maternal blood can be used for the reliable determination of foetal single-gene disorders, especially for haemoglobinopathies. This work is carried out in continuation of our involvement with the Framework Program 6 (FP6) project SAFE and builds on our NIPD service provision for X-linked disorders and for the prevention of the haemolytic disease of the newborn.

ITHANET - electronic infrastructure for thalassaemia research network

ITHANET was conceived as a Euromediterranean network of research centres conducting molecular and clinical research on thalassaemia and related haemoglobinopathies. The ITHANET consortium comprises all major European research institutions active in the field and a number of collaborating partner institutions from non-EU Mediterranean and Black-Sea countries. The original FP6 project ITHANET associated 25 partners from 16 countries, with the CING as coordinator, and included scientific and medical communities, patients and their families, and patient associations. The work of ITHANET is continued through further development of the ITHANET portal (www.ithanet.eu) by the Molecular Genetics of Thalassaemia Department, in interaction with our partners in the field.

ITHANET aims to strengthen research and treatment of haemoglobinopathies by:

1. creating an inclusive research environment
2. promoting common research strategies and resources
3. facilitating the dissemination of research results
4. improving quality and availability of health care services

Hepat-omics project

Identification of novel peripheral blood biomarkers for liver disease in β-thalassaemia patients through the use of ‘omics’ technologies.

This project aims primarily to identify potential non-invasive, novel serum diagnostic biomarkers for different stages of liver disease (fibrosis and cirrhosis) in β-thalassaemia patients using combined data from proteomics, metabolomics and transcriptomics. This project is funded by the national Research Promotion Foundation/ Research and Innovation Foundation under the RESTART Programs 2016 – 2020/ Excellence Hubs (EXCELLENCE/0918/118).

Haemomics project

Omic studies of the mechanism of activation of γ-globin for the treatment of haemoglobinopathies

The project aims to the identification of new proteins involved in the regulation of γ-globin gene expression with the intention of identifying suitable pharmacological targets for the treatment of β-haemoglobinopathies (β-thalassaemia and sickle cell disease). Reactivation of γ-globin for the production of fetal haemoglobin (HbF) has long been recognized as a very promising therapeutic approach, since the phenotype of patients with β-thalassaemia or sickle cell disease can be ameliorated. The project is funded by the national Research and Innovation Foundation (RIF) under the RESTART Programs 2016-2020/Excellence Hubs (EXCELLENCE/1216/0389).

 

 

 

 

Publications

  Patsali P, Papasavva P, Stephanou C, Christou S, Sitarou M, Antoniou MN, Lederer CW, Kleanthous M. Short-hairpin RNA against aberrant ...

Grants Obtained

GenoMed4ALL (Genomics and Personalized Medicine for all though Artificial Intelligence in Haematological Diseases) – 101017549, 2021-2024. Funded by ...

Awards

Όνομα Οργανισμός Βραβείο Carsten W. Lederer Συνέδριο Ευρωπαϊκού Πανεπιστημίου Κύπρου, Κύπρος, 2019 1ο βραβείο για ...

Collaboration Networks

  1. ThalaMoSS (www.thalamoss.eu) THALAMOSS (Thalassaemia Modular Stratification System for personalized therapy of β-thalassemia) is aimed at ...

RESTORE

RESTORE - the Large-Scale Research Initiative for Advanced Therapies in Europe   We at the Cyprus Institute of Neurology & Genetics are part of ...

Hepat-omics project

Identification of novel peripheral blood biomarkers for liver disease in β-thalassaemia patients through the use of ‘omics’ technologies.

Haemomics project

Haemomics project – Omic studies of the mechanism of activation of γ-globin for the treatment of haemoglobinopathies   The project aims to the ...

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