Belgian National Node

Belgium is involved in the EPTRI project collaborating in several work packages and in the Thematic Research Platform on “Paediatric Biomarkers and Biosamples” as “Antwerp University” and “Antwerp University Hospital”.

Belgian respondents of the EPTRI WP3 surveys described expertise in “Paediatric Medicines Discovery” (44,45%) in neonatal and paediatric intensive care, neonatology, gastroenterology, endocrinology, gynaecology, nutrition, cardiology, vascular diseases, hepatology, infectious diseases, nephrology, urology, neurology, ophthalmology and rheumatology; in “Paediatric Biomarkers and Biosamples” (11,1%) in neonatology, neonatal and paediatric intensive care, cardiology, vascular diseases, gastroenterology, haematology, immunology, musculoskeletal diseases, nephrology, urology, neurology, nutrition, pulmonary and respiratory diseases; in “Developmental Pharmacology” (44,45%) mainly in neonatology, neonatal and paediatric intensive care, cardiology, vascular diseases, endocrinology, gynaecology, gastroenterology, haematology, immunology, infectious diseases, musculoskeletal diseases, nephrology, urology, neurology, nutrition, ophthalmology, oncology, pulmonary and respiratory diseases.

During the first months of the 2020, EPTRI received the letter of support from Antwerp University Hospital, Antwerp University, Ghent University, and Katholieke Universiteit Leuven.

Moreover, the Institutes mentioned above and the Cliniques Universitaires Saint-Luc, Université catholique de Louvain, University Hospital Liège, Institut de Pathologie et de Génétique and Hôpital Universitaire des Enfants Reine Fabiola are involved in the Memorandum of Understanding to support the development of the EPTRI Infrastructure and organise themselves into a National Node (the Belgian Hub) to link, guide and coordinate the Belgian scientific community in EPTRI.

The Belgian Hub (EPTRI-BE) will be led by the “Ghent University” and will be constituted by the following Institutions. More details are provided below:

• Antwerp University: The researchers are engaged in the fields of neonatology, neonatal and paediatric intensive care, gastroenterology, infectious diseases, nutrition, oncology, pulmonary and respiratory diseases. They develop new model platforms using zebrafish and perform developmental molecular and experimental pharmacology. The Research Units (RUs) study in vitro drug metabolism in zebrafish embryo homogenates and in liver microsomes from juvenile minipig. Moreover, they explore the use of minipig as a preclinical model for paediatric drug research and development of physiologically based pharmacokinetic model. At the Laboratory of Experimental Medicine and Paediatrics, the researchers perform identification and characterisation of biomarkers used as prognostic tools in paediatric diseases using flow cytometry, qPCR, and ELISA technique. In particular, they use volatile organic compounds as possible marker for bronchopulmonary dysplasia, and they study adipokine secretions (leptin, adiponectine, TNF, IL-6) in the context of obstructive sleep apnea and obesity. Furthermore, the University has a decentralised biobank with a sector dedicated to paediatric biosamples.
• Antwerp University Hospital: At the Department of Experimental Medicine and Paediatrics, the researchers study pneumology (e.g. sleep related disorders, bronchopulmonary dysplasia and cystic fibrosis using novel imaging techniques); cardiovascular diseases in patients with specific diseases such as Down syndrome and obesity; infectious diseases (e.g. respiratory syncytial virus infection in children to search of predictive factors of the severity in this infection). The RUs also study the developmental mechanisms in immunology (e.g. asthma) and neurology (e.g. head injury). In particular, the RUs study the effects on neuroinflammatory diseases on mouse neural stem cell. In the field of nutrition, the researchers investigate different metabolic and rare disorders including mucopolysaccharidosis, phenylketonuria, Fabry disease, urea cycle disorders, Crigler-Najjar syndrome and intoxication type metabolic disease.
• Cliniques Universitaires Saint-Luc: The Paediatric Research unit focuses its research on endocrinology, gynaecology, gastroenterology, hepatology, nutrition, and immunology (e.g. asthma). The researchers develop new model platforms using placental and umbilical cord, 3D organoid cell cultures from paediatric samples, and stem cell as liver derived stem cells, pancreatic stem cells and stellate cells which are used also in regenerative medicine and in tissue engineering approaches. They study neurology diseases such as Dravet syndrome caused by loss of function in Scn1a gene inducing epileptic encephalopathies. They also perform experimental validation of novel paediatric drug targets, research of predictive markers of diabetes, animal models study for biliary and toxic liver diseases, and histology and tissue imaging.
• Université catholique de Louvain: At the Department of Gynaecology, Obstetrics and Paediatric, the researchers have expertise mainly in gynaecology, neonatology, oncology and hepatology. They study paediatric development mechanism in immunology (e.g. asthma) and in hormonal research (e.g. the role of the growth factors). They work also on stem cell biology for regenerative medicine and on transplantation. The researchers use in vitro models (e.g. endothelial tissue, liver cell cultures and ovarian tissue) to study the different expression of the growth factors, and to conduct fertility studies. Moreover, they use animal models (e.g. pig and mouse) for pre-clinical studies. They perform pharmacokinetic and pharmacodynamic studies to investigate the effects of chemotherapy on placental developmental. They are also engaged in tumour study (cervical cancer), in genes expression and genomic approaches to identify mutations involved in well-known syndromes.
• Hôpital Universitaire des Enfants Reine Fabiola: The researchers focuses their research on several field as haematology on hematopoietic stem cell transplantation for sickle cells; neurology on epileptic syndromes; oncology on leukaemia and clinical trials on rhabdomyosarcoma; infectious diseases on molecular epidemiology, ecology and the evolution of group A of Streptococcus bacterium (its infection and its possible vaccine), and also on Helicobacter pylori; genetics on genes that can cause epileptic disorders, developmental disorders, intellectual disability and on congenital diseases. The researchers study immunotherapy, and use flow cytometricand animal models to conduct their studies (e.g. rabbit).
• Katholieke Universiteit Leuven: At Katholieke Universiteit Leuven the research is very prolific on neonatology, cardiology, nephrology, urology, pulmonary and respiratory diseases. In particular, they study developmental mechanisms in pulmonary hypertension and lung hypoplasia, immunology (e.g. asthma), neurology (e.g. movement disorders, infant brain atlas), oncology (e.g. neuroblastoma) and infection (e.g. encephalopathy). They develop new model platforms using placental and umbilical cord, 3D organoid cell cultures from paediatric samples, zebrafish models, rabbit models, nasal ciliary activity models, renal tubular cell models (Fanconi syndrome, cystinosis) and renal cell models. Moreover, they study stem cell biology on stem cell harvested from foetal/neonatal urine and amniotic fluid to cure congenital diaphragmatic hernia, lung and kidney. They also try to identify novel drug targets on tracheal fluid in congenital diaphragmatic hernia setting. The researchers work on the developmental molecular and experimental pharmacology in animal models (as mice, rabbit and zebrafish). Their researches are also aimed at identifying, characterizing and validating the paediatric biomarkers used as diagnostic, prognostic and predictive tools, but also as drug targets, developmental stage markers and safety markers. They also perform sensitive biofluids assays using different type of techniques as liquid chromatography–mass spectrometry/mass fingerprinting to identify the sequences of individual peptides, high-pressure liquid chromatography, proteomics, metabolomics, pharmacometrics and pharmacogenetics studies.
• Ghent University: At the Department of Basic and Applied Medical Sciences, the researchers study neonatology, neonatal and paediatric intensive care, haematology, infectious diseases, nephrology, and urology. The researchers are specialized in microdosing, in pharmacometrics in different age groups, in different diseases and in different ethnic groups, and in marker test techniques using renal biomarkers to explore variability in drug disposition and effects as adverse drug reactions. They perform renal function estimation methods and develop new pharmacokinetic and pharmacodynamics (PK-PD) models in neonatal and paediatric intensive care children. At Department Pharmacology, Toxicology and Biochemistry and at the Department of Bioanalysis, the researchers investigate neonatal and paediatric intensive care, immunology, nephrology, and urology. They use in vitro models of hepatocytes, hepatic and renal microsomes, and renal transporters. They carry on juvenile animal studies (as on pig model), sensitive biofluids assay (dry blood spot, microsampling) and population PK-PD studies, and physiologically based pharmacokinetic modelling analysis across the different paediatric age groups. They use mathematical PK-PD modelling and simulation in support of dose regimen selection, formulation choice and study design.
• University Hospital Liège: At the Departments of Paediatrics, the RUs study cardiology, vascular diseases, immunology, oncology, pulmonary and respiratory diseases, rheumatology, and endocrinology. Their research involves paediatric development mechanisms in oncology (e.g. neuroblastoma, and epigenetics) and hormonal research (e.g. infancy growth, onset of puberty). In particular, they study the effects of several disorders in children with gonadotropin deficiency, neuroendocrine disruption, craniopharyngioma and Syndrome of Klinefelter. They also perform identification and characterization of biomarkers used as diagnostic and prognostic tools and as developmental stage marker (miRNA and exosomes in myocardial fibrosis in congenital diaphragmatic hernia and rheumatic disorders). The researchers also perform experimental and human studies on the pathophysiology of myocardial remodelling in congenital cardiac defects. Another branch of research at the University Hospital Liège is the study of the role of the inflammatory cytokines, the mediators of cellular growth and the apoptosis regulators in a neonatal model of pulmonary stenosis.
• Institut de Pathologie et de Génétique: It is specialised in anatomical pathology, clinical genetics, and molecular and cell biology medical diagnosis. The aim of anatomical pathology groups is to establish a precise diagnosis based on smears and material from cytological punctures, endoscopic biopsies or surgical specimens for many pathologies as infection, inflammation, and benign and malignant tumours (e.g. oncopathology). At the Department of Molecular and Cell Biology, researchers are interested in onco-haematology diseases, molecular diagnosis of different hereditary or acquired human pathologies with different approaches and cytogenetic technologies. They work on characterisation, genotyping, and phenotyping of genes, cancer genetics, structural variations, and copy number variation. They also perform classic cytogenetics, fluorescence in situ hybridisation, comparative genome hybridisation, next-generation sequencing and non-invasive prenatal testing.