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Lut Van Laer
- Research Expertise:My expertise is situated within cardiogenetics, more specifically within molecular cardiogenetics. Cardiogenetics include the following disorders: thoracic aortic aneurysm and dissection, primary electrical diseases, cardiomyopathy and familial hypercholesterolemia. Sudden cardiac death is an important cause of death with an annual incidence of one death per 1000 person-years. Above the age of 45 years sudden cardiac death is usually due to atherosclerotic coronary disease, however below the age of 45 years often hereditary heart diseases are responsible for the sudden death. The four most frequent causes within this age group are premature atherosclerosis (for example familial hypercholesterolemia), cardiomyopathy (for example hypertrophic cardiomyopathy), primary electrical diseases (for example long-QT or Brugada syndrome) and aortic dissection. The objective of our research is to recognize the cause of the sudden death in individuals younger than 45 years of age, to identify the role of hereditary causes and to define the best strategy for diagnostics and prevention. Our main focus lies on the genetic etiology of aortic aneurysms and primary electrical diseases. Aortic aneurysms and dissection/rupture is an important health problem in the Western world with an estimated mortality of 1-2%. The current knowledge on aortic aneurysms was generated mostly based on the study of rare monogenic forms of thoracic aortic aneurysms (TAA), such as Marfan syndrome (MFS) and Loeys-Dietz syndrome (LDS). Through the identification of the genetic basis of LDS and the study of mouse models for MFS, a key role for the dysregulation of the TGFβ signaling pathway in the pathogenesis of TAA was discovered. Subsequently, dysregulation of TGFβ signaling was also demonstrated for other syndromic and non-syndromic forms of TAA. With our research we try to identify new causal genes for TAA, to elucidate the related pathogenic mechanisms and to further explore the role of dysregulated TGFβ signaling in the development of TAA. Primary electrical diseases consist of a group of mostly autosomal dominant disorders that are characterized by disturbed action potentials in the heart that can lead to sudden cardiac death at a young age. Although more than 50 genes have been associated with these disorders, the exact causal gene remains elusive in approximately 70% of the patients. Moreover, these hereditary cardiac arrhythmias are genetically and phenotypically heterogeneous and, in addition, a lot of variants of uncertain significance are found within the molecular diagnostic setting. This hampers an exact risk assessment and as a consequence also an efficient preventive and therapeutic policy for the patient. We aim to tackle these problems through the identification of new causal genes and to develop new diagnostic tools that allow to characterize the functional and phenotypic effect of genetic variants.
- Keywords:CARDIOGENETICS, Biomedical sciences (incl. biochemistry)
- Disciplines:Molecular diagnostics, Cardiac and vascular medicine not elsewhere classified
- Research techniques:Next generation and Sanger sequencing, molecular techniques, functional studies
- Users of research expertise:cardiogenetic research laboratories, patients, patient organisations