Research topics

Prinicipal Investigators: Bart Loeys, Aline Verstraeten, Maaike Alaerts, Josephina Meester & Lut Van Laer

Background

​The aorta serves as the artery responsible for the distribution of oxygen rich blood from the heart towards the distal parts of the human body. A pathological expansion of the thoracic aorta is called a thoracic aortic aneurysm and entails a high risk for aortic dissection and/or rupture. The latter events associate with severe internal bleedings, often resulting in sudden death. To date, genetic defects in more than 35 genes have been linked with thoracic aortic aneurysm/dissection, explaining about 30% of patients with thoracic aortic aneurysm/dissection. Identification and functional characterization of these disease genes have been key in acquiring our current aortopathy knowledge and delivering novel decelerating therapeutic agents. Medical therapies capable of completely stopping or even reversing aneurysm formation are not yet available though.

Goal

We aim to contribute to the further elucidation of the genetic and mechanistic landscape of thoracic aortic aneurysm as well as to develop novel therapies, with the ultimate goal of improving patient management. The ongoing research lines are contrived in such a way that their results are expected to increase the molecular diagnostic yield, to improve genetic counseling, and to identify predictive markers and curative therapies. ​

Strategy

​The lab has a longstanding tradition in the use of DNA sequencing technologies in affected individuals from families that are negative for mutations in the known genes to find novel thoracic aortic aneurysm genes. For a selection of these genes, we seek to profoundly map the downstream functional consequences and to pinpoint novel drug targets and/or genuine read-outs for drug testing. Novel candidate drug options ensuing from the latter experiments are subsequently tested in pre-clinical disease models. In addition, an important research line on the discovery and first-line functional characterization of genetic aortopathy modifiers is also established. Individuals belonging to the same family and carrying the same primary mutation can namely range from completely asymptomatic to sudden death at young age due to dissection, considerably complicating patient counselling. Besides traditional molecular biology approaches, the current projects involve the use of state-of-the-art techniques such as whole exome sequencing, whole genome sequencing, transcriptomics and interactomics/proteomics in patient samples, induced pluripotent stem cell-derived vascular smooth muscle cells and/or mouse models.

Disorders under investigation

Marfan syndrome, Loeys-Dietz syndrome, Meester-Loeys syndrome, IPO8-related aneurysm syndroom, vascular Ehlers-Danlos syndrome, arterial tortuosity syndrome, bicuspid aortic valve related thoracic aortic aneurysm syndrome, familial thoracic aorta aneurysm syndrome.

Prinicipal Investigators: Bart Loeys & Maaike Alaerts

Background

​Inherited primary cardiac arrhythmia disorders are an important cause of sudden cardiac death, especially when this is occurring in young individuals. Research already enabled identification of more than 60 genes associated with these disorders, but in more than half of the patients no mutations are detected in any of the known genes and the genetic cause remains elusive. Through study of these disease genes new insight has already been gained in the pathophysiological mechanisms causing primary arrhythmias, but the picture remains far from complete. For the moment there are no therapies available that can cure the arrhythmias, only implantation of a cardioverter defibrillator can completely abolish the risk for sudden cardiac death.

Goal

We aim to further investigate the genetic causes and disease mechanisms underlying cardiac arrhythmias. This will lead to a significantly improved understanding of the disorders and provide the possibility to develop novel therapies. With our research team we aim to improve genetic diagnosis, risk prediction, optimize counseling and deliver true personalized management of patients to increase their quality of life. ​​

Strategy

Using modern DNA sequencing techniques (including whole-exome and whole-genome sequencing) in patients without a genetic diagnosis, we will identify novel genes involved in arrhythmias. We are also focusing on the identification of genetic modifiers that play a role in the development of these disorders and can explain the phenotypic variability observed within families. The functional effect of mutations in these genes and modifiers are studied in patient samples, induced pluripotent stem cell (iPSC)-derived cardiac cells and transgenic zebrafish or mice. Hereto we are using state-of-the-art techniques such as CRISPR/Cas genome editing, transcriptomics, interactomics, proteomics, high-tech microscopy and micro-electrode arrays. Based on these novel insights, new therapeutic targets can be identified for which novel drugs can be tested in the pre-clinical disease models that we generated.

Disorders under investigation:

Brugada syndrome, Short and Long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, RYR2 related calcium release deficiency syndrome

Principal Investigator: Bart Loeys & Maaike Alaerts

Background

​Cardiomyopathies are disorders of the heart muscle, resulting in improper contraction and/or relaxation of the heart. This can lead to cardiac arrhythmias, heart failure and even sudden cardiac death, sometimes in young individuals. Often these cardiomyopathies are inherited and research already enabled identification of more than 60 genes associated with these disorders. But in more than half of the patients no mutations are detected in any of the known genes and the genetic cause remains elusive. Through study of these disease genes new insight has already been gained in the pathophysiological mechanisms causing cardiomyopathies, but the picture remains far from complete. At present, there are some therapeutic options to reduce disease symptoms, but therapies that are capable of completely stopping or even reversing the disease are not yet available.

Goal

We aim to further investigate the genetic causes and disease mechanisms underlying cardiomyopathies. This will lead to a significantly improved understanding of the disorders and provide the possibility to develop novel therapies. With our research team we aim to improve genetic diagnosis, risk prediction, optimize counseling and deliver true personalized management of patients to increase their quality of life. ​

Strategy

​Using modern DNA sequencing techniques (including whole-exome and whole-genome sequencing) in patients without a genetic diagnosis, we will identify novel genes involved in cardiomyopathies. We are also focusing on the identification of genetic modifiers that play a role in the development of these disorders and can explain the phenotypic variability observed within families. The functional effect of mutations in these genes and modifiers are studied in patient samples, induced pluripotent stem cell (iPSC)-derived cardiac cells and transgenic zebrafish or mice. Hereto we are using state-of-the-art techniques such as CRISPR/Cas genome editing, transcriptomics, interactomics, proteomics, high-tech microscopy and micro-electrode arrays. Based on these novel insights, new therapeutic targets can be identified for which novel drugs can be tested in the pre-clinical disease models that we generated.

Disorders under investigation:

Hypertrophic cardiomyopathy, dilated cardiomyopathy, arrhythmogenic cardiomyopathy, non-compaction cardiomyopathy.

Principal Investigator: Aline Verstraeten, Bart Loeys & Josephina Meester

Background

Chondrodysplasias are rare genetic disorders affecting the hyaline cartilage. This cartilage tissue is found in several areas of the human body, including the ears, nose, ribs, joint surfaces. It has an important function in the growth plate, the location in the bone where longitudinal growth takes place. Hyaline cartilage also forms the temporary skeleton during embryogenesis, which is gradually replaced by bone. Chondrodysplasia patients are clinically characterized by skeletal manifestations such as bone and joint deformities of the limbs, trunk, and skull as well as varying degrees of dwarfism. More than 400 different chondrodysplasias have been identified so far. In the last decade, the application of the massively parallel sequencing technology has boosted the discovery of the underlying genetic defect for many of these disorders, resulting in the identification of more than 400 different disease genes. However, to date, the downstream effects of these genetic defects remain largely unknown. Furthermore, no pharmacological treatment exists for many chondrodysplasias and current surgical treatment options (such as limb lengthening) are often highly invasive and have a major impact on a child's life. With many patients and families seeking for better treatment options, new pathomechanistic and preclinical research is urgently needed.

Goal

With our research we aim to provide new pathomechanistic insights in chondrodysplasias, and enable the development of new therapeutic strategies to treat patients with chondrodysplasias. As such we want to improve the quality of life of patients with chondrodysplasias.

Strategy

In our ongoing research projects, we use state-of the-art techniques (such as transcriptomics, interactomics, proteomics) in both mouse models and patient-specific induced pluripotent stem cell (iPSC)- derived chondrocyte models of different chondrodysplasias to gain pathomechanistic insights in these disorders. Based on these new insights, novel therapeutic targets and drug compounds are selected and tested in pre-clinical disease models.

Recently, we are also focusing on the comparison of pathomechanisms of both the vascular and skeletal system in chondrodysplasias and aneurysmal thoracic aortopathy, as increasing evidence suggests an important molecular and functional intersection between both organ systems in these phenotypically distinct disorders.

Disorders under investigation

COL2A1-related chondrodysplasias (Stickler syndrome, spondylo-epiphyseal dysplasia congenita), BGN-related chondrodysplasia (X-linked spondyloepimetaphyseal dysplasia), Marfan syndrome

Principal Investigator: Marije Meuwissen, Anna Jansen, Bart Loeys & Sarah Weckhuysen

Background

Disorders of brain functioning are heterogeneous, but result in common effects with detrimental consequences in daily life. Disorders of brain functioning can be either developmental or occur later in life, i.e. after a brain hemorrhage or trauma. The main focus of our group is to unravel the genetic causes of developmental brain disorders and more specifically those causing cerebral palsy (CP). CP is the leading cause of motor impairment in children due to damage in the developing brain. It is often accompanied by a wide range of medical conditions such as intellectual disability, learning difficulties, speech and language deficits, epilepsy, autism spectrum disorder and visual and/or hearing impairment. Perinatal oxygen deprivation was long thought to be the leading cause of CP, but recent studies demonstrate this as a cause in at most 12% of patients and genetic causes of CP are increasingly being discovered. However, insights into underlying mechanisms leading to CP are still limited.

A subgroup of disorders that lead to CP are cerebrovascular disorders, e.g. COL4A1- and COL4A2-related disorders. In these disorders, a weakening of the cerebral blood vessels leads to an increased risk of cerebral hemorrhage; this can occur already during pregnancy or in early childhood, but in other patients, the disorder presents only at a later age, e.g. with intracranial aneurysm (widening of the blood vessels of the brain). The underlying mechanism of cerebrovascular disease associated with COL4A1- and COL4A2-variants in both CP and adult-onset intracranial aneurysms is still not fully understood. In addition, studies focused on the identification of additional genetic factors in both infantile and adult cerebrovascular disorders, including intracranial aneurysms, may contribute to unravel underlying pathomechanisms.

Malformations of cortical development (MCD) constitute of a group of rare congenital brain malformations that can also present as CP and associated features. Disorders in the MCD spectrum include lissencephaly (smooth brain), heterotopia (aberrantly located bands or clusters of neurons), and polymicrogyria (multiple small convolutions of the cerebral cortex) with or without microcephaly (small brain) or megalencephaly (large brain). Despite a significant effort in the identification of genetic causes underlying MCD, 60% of MCD cases currently remain molecularly unexplained. Alternative molecular diagnostic approaches are needed to increase the genetic uptake in MCD patients. Additionally, for this subtype of brain disorders, a better understanding of mechanisms involved will be crucial to make steps forward in improvement of care and treatment.

Goal

Our research focuses on deciphering the genetic background and underlying pathomechanisms of these subgroups of brain disorders. We strongly believe that our research contributes to diagnosis and improvement of patient care and can be the entry point for the development of novel targeted therapies.

Strategy

We use state-of-the-art approaches including exome and genome sequencing and transcriptomics to gain insight into the molecular background and pathomechanisms of these groups of disorders. In vivo modelling of COL4A1- and COL4A2-related disorders is also part of our portfolio.

Disorders under investigation

COL4A1- and COL4A2-related disorders, cerebral aneurysm, cerebral palsy, KIF1A-related NESCAV syndrome, malformations of cortical development, mTORopathies, tubulinopathies

Principal Investigator: Ken Op de Beeck, Guy Van Camp & Erik Fransen

The oncogenetics program led by Prof. Dr. Guy Van Camp and Prof. Dr. Ken Op de Beeck encompasses a broad and highly integrated research effort aimed at understanding the molecular mechanisms that drive cancer initiation, progression, and therapeutic response. Their work focuses on dissecting the genetic, epigenetic, and transcriptomic alterations underlying multiple tumor types, including colorectal cancer, mesothelioma, pancreatic neuroendocrine tumors, lung cancer, cervical cancer, and pan-cancer epigenomic signatures.

A central theme within the group’s research portfolio is the discovery and clinical translation of biomarkers for early cancer detection, prognosis, and treatment monitoring. The team has pioneered the development of DNA methylation-based biomarkers, identifying large sets of differentially methylated sites across various cancer types using advanced bioinformatics analyses. Their laboratory has engineered patented high-throughput assays capable of detecting multiple methylation markers simultaneously in liquid biopsies, dramatically expanding diagnostic capabilities for minimally invasive cancer screening.

These innovations extend into several major research programs. In colorectal cancer, the team contributes to the development of multi-regional methylation assays designed for early detection and enhanced treatment follow-up. Their work also supports multiplex ddPCR-based assays capable of detecting multiple cancer-specific signals in a single reaction, enabling efficient multi-cancer screening strategies.

The research on mesothelioma includes the creation of biomarker tools for improved screening, treatment response monitoring, and organoid-based modeling of therapy resistance. By integrating patient-derived organoids with liquid biopsy-based methylation and mutation profiling, the team investigates mechanisms of delayed diagnosis and therapeutic failure in this challenging tumor type.

The group’s interest in pan-cancer methylation markers has led to genome-wide initiatives aimed at identifying universal and cancer-type–specific epigenetic signatures. These studies involve large-scale computational analysis and often leverage multi-omics datasets to refine models of tumor classification and improve diagnostic accuracy across diverse cancers. The inclusion of postdoctoral and PhD-level bioinformatics specialists significantly enhances the team’s data analysis capabilities.

Beyond epigenetics, the team explores oncogenic signaling pathways and genomic alterations across several cancer entities. In lung cancer research, they contribute to projects focused on ROS1-positive non-small cell lung cancer, with goals to improve rational therapy selection using patient-driven research frameworks. Cervical cancer investigations include efforts to develop combined screening and molecular triage approaches integrating HPV detection, viral load quantification, genotyping, and methylation profiling using self-sampled material.

The research infrastructure supporting these activities includes next-generation sequencing platforms (Illumina HiSeq, NextSeq, MiSeq), microarray systems, and advanced computational environments for exome, genome, transcriptome, and methylation data analysis. The team’s strong bioinformatics expertise enables precise variant annotation, epigenomic mapping, machine-learning–assisted biomarker discovery, and integration of multi-omics datasets from sources such as TCGA.

Overall, the oncogenetics research program represents a dynamic and translationally oriented effort at the interface of genomics, epigenetics, biomarker science, and precision oncology. Through clinical partnerships, interdisciplinary collaboration, and continuous methodological innovation, the team contributes to a more refined understanding of cancer biology and to the development of next-generation molecular diagnostics with tangible clinical impact.

Principal Investigator: Erik Fransen, Ken OP de Beeck & Guy Van Camp​

The research team jointly led by Prof. Dr. Guy Van Camp and Prof. Dr. Ken Op de Beeck has built an internationally recognized expertise in the field of hereditary hearing impairment, with a particular focus on nonsyndromic sensorineural hearing loss and otosclerosis. For several decades, the team has contributed to defining the genetic architecture of auditory disorders, and their work remains closely integrated with the Medical Genetics diagnostics department, a major national and European reference center for hereditary hearing loss.

The group uses genome-wide approaches, including next-generation sequencing, microarrays, and advanced bioinformatics pipelines, to identify disease-causing variants and regulatory mechanisms influencing auditory function. A central line of research involves characterizing key genes implicated in hearing loss. Among these, the COCH gene—which is responsible for late-onset progressive hearing impairment in many Belgian families—has been the focus of collaborative investigations with Otolaryngology UZA, aiming to explore gene therapy-based interventions as future treatment options.

In addition to sensorineural hearing loss, the team studies otosclerosis, a disorder of abnormal bone remodeling in the otic capsule that can lead to conductive or mixed hearing loss. Recent research has highlighted the role of extracellular matrix components in otosclerosis, including aggrecan, a large proteoglycan involved in cartilage structure and biomechanical stability. While otosclerosis has long been regarded as a disease with both genetic and environmental components, the identification of molecular pathways involving aggrecan and related matrix regulators opens new avenues for understanding disease progression and for developing diagnostic markers.

Overall, the group combines deep clinical connections with cutting-edge molecular research, enabling the continuous translation of genetic discoveries into improved diagnostic practices and future therapeutic prospects for hereditary hearing impairment and otosclerosis.

Principal Investigator: Wim van Hul

Background

Osteoporosis is the most common metabolic bone disorder, characterized by a decreased bone mass resulting in an increased fracture risk. It is a multifactorial disease with environmental factors contributing but also the heritability is high, indicating an important role for genetic factors. In the last decade, a lot of novel genes and associated pathogenic mechanisms have been identified by studying monogenic conditions with an abnormal bone mass. These include the sclerosing bone dysplasias in which patients have an increased bone mass.

Goal

We aim to identify novel genes and genetic variants that are causal for increased bone mass in monogenic sclerosing bone dysplasias. The unravelling of these pathogenic mechanisms is of relevance for the patients but could also result in gained insights into the homeostasis of bone mass in the general population and in patients diagnosed with osteoporosis.

Strategy

DNA sequencing is performed on DNA from patients with an abnormal bone mass. The approach can range between sequencing candidate genes, the use of a (virtual) gene panel or whole exome of genome sequencing. Genetic variants of potential relevance are validated by in vitro functional studies or by construction and phenotyping of animal models including mouse and zebrafish models.

Disorders under investigation

Paget's disease

​Principal Investigator: Wim van Hul

Background​

Obesity is an important health risk with an increasing prevalence. It is associated with fat accumulation in adipose tissue as well as ectopically in tissues such as liver and skeletal muscle. Ectopic fat accumulation in the liver (Non-Alcoholic Fatty Liver Disease, NAFLD) can be accompanied by chronic liver necroinflammation (Non-Alcoholic Steatohepatitis, NASH). It has become clear that NAFLD/NASH is not just a consequence of obesity, but is a driving force of both metabolic and cardiovascular derangements. The mechanisms and processes underlying the development of obesity are undoubtedly multifactorial in nature. First, numerous studies have shown that 40-70% of the interindividual variability in BMI can be attributed to genetic factors. Given the estimated heritability, extensive genome-wide association studies (GWASs) have been performed to identify common single-nucleotide polymorphisms (SNPs) possibly underlying the heritable risk for human obesity. Despite the fact that a large number of associated variants were identified, they only explain a small percentage of the genetic variability. Second, the dramatically increasing prevalence cannot be explained exclusively by genetic factors. The same holds true for NAFLD/NASH, for which several SNPs have been identified that, as background modifiers, explain part of the interindividual variation in presence and severity of these liver pathologies.

Goal

The aim of the research is to study the effect of genetic variants on the risk for obesity and their contribution in the development and progression of NAFLD/NASH.

Thanks to long lasting clinical collaborations, samples from large cohorts of patients are available for study. A multi-omics approach is used including genomics, epigenomics and transcriptomics to identify and characterize genetic variants that could contribute to the pathogenesis of obesity and associated liver diseases. Furthermore in vitro functional studies are performed as well as zebrafish models are made to validate variants of potential interest.

Disorders under investigation

Non-Alcoholic Fatty Liver Disease

​Principal Investigator: Frank Kooy

Mission

Our mission is to identify genetic causes of cognitive disorders and to study the molecular defects in order to eventually develop rational therapy.

Embedding

Our research group Cognitive Genetics is part of unit Medical Genetics of the Faculty of Pharmaceutical, Biomedical and Veterinary Sciences of the University of Antwerp. In combination with diagnostic administrative and clinical units the research unit forms the Center of Medical Genetics. We are part of the University of Antwerp research excellence center GENOmics in MEDicine (GENOMED), that was recently awarded a prestigious Methusalem grant. Our group is also a founding member of the expertise technology consortium Precision Medicine Technologies (PreMeT) for logistic support of our industrial collaborations.

What we do

Our research has focussed on intellectual disability and syndromic forms of autism. Both disorders are frequent. For example, intellectual disability is estimated to affect 2-3% of the total population, while autism rates appear to be increasing, with reported prevalence as high as 1 in 44. Both disorders have a strong genetic component, that remains unveiled in the majority of cases. As the causes of the cognitive disorders are genetically extremely heterogeneous, the identification of the cause of the disorder requires an approach specific for this type of disorder.

We identify novel causes of cognitive disorders starting from rare, affected patients or families and from patients with specific chromosomal abnormalities, including microdeletions, translocations and fragile sites. To achieve this, we are constantly incorporating and optimizing the latest technologies relevant for our search and are also developing novel technologies. For the functional study of the genes of interest, we rely on animal and cellular disease models.

For example, our functional research on the knockout mouse model of Fragile X syndrome—a common cause of cognitive impairment and autism—led to human drug trials, offering hope for targeted treatments. To further enhance our understanding of the disease's molecular basis, we replicate disease-related mutations in human embryonic stem cells. These cells are then differentiated into various types of brain cells, known as neurons, allowing us to study the disorders in disease-relevant tissue.

Disorders under investigation

Helsmoortel-Van der Aa syndrome