Sander Houten, PhD
- ASSOCIATE PROFESSOR | Genetics and Genomic Sciences
Research Topics:Genetics, Mitochondria
Dr. Sander M. Houten has a Ph.D. from the faculty of Medicine of the University of Amsterdam where he worked on inborn errors of metabolism and discovered that a deficiency of mevalonate kinase causes hyper-IgD syndrome. For his postdoctoral studies, he moved to the Institut de Génétique et de Biologie Moléculaire et Cellulaire in Strasbourg, France and worked on mechanisms underlying the control of metabolism in vivo in mouse models and defined a novel bile acid signaling pathway via a G-protein-coupled receptor that increases energy expenditure. He then returned to the Academic Medical Center of the University of Amsterdam to develop his own research line on the pathophysiology of inborn errors of mitochondrial fatty acid oxidation in the laboratory Genetic Metabolic Diseases. He is currently an associate professor for the Department of Genetics and Genomic Sciences, and will continue his research on fatty acid oxidation defects with the aim to develop new therapeutic options. In collaboration with the Icahn Institute for Data Science and Genomic Technology, he will try to identify molecular markers of disease severity in inborn errors such as fatty acid oxidation disorders with the ultimate aim to find new disease modifiers.
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Multi-Disciplinary Training AreaGenetics and Data Science [GDS]
MSc, University of Amsterdam
PhD, University of Amsterdam
Neil Buist Award
Wadman – Van Gennip award
Network medicine for inborn errors of metabolism
Despite their seemingly monogenetic nature, many inborn errors of metabolism, such as fatty acid oxidation disorders, have a remarkably heterogeneous clinical presentation making the disease course and severity difficult to predict. In fact, from a contemporary perspective there is no clear distinction between simple Mendelian disorders and complex diseases such that collectively these disorders represent a continuum of diminishing effects from a single gene influenced by modifier genes to increasingly shared influence by multiple genes. This realization highlights the need for an unbiased approach to finding candidate modifier genes for seemingly ‘monogenetic’ diseases and reveals the possibility of applying an experimental model system ‘designed’ for complex diseases to inborn errors of metabolism. Our preliminary research is demonstrating that experimental model systems successfully utilized to advance our understanding of complex disease (e.g. genetics of gene expression data in complex genetic reference populations of mice) are equally useful in advancing our understanding of inborn errors of metabolism, in particular by revealing the molecular networks underlying inborn error disease severity.
Fatty acid oxidation disorders
Mitochondrial fatty acid beta-oxidation (FAO) plays a crucial role in energy homeostasis of organs such as liver, heart and skeletal muscle. During fasting when glucose supply becomes limited, FAO is a vital energy source. For most FAO enzymes, a recessively inherited defect is known, leading to an overall high cumulative incidence (~1 in 10,000). Typical clinical features of these FAO defects are fasting-induced hypoketotic hypoglycemia, and cardiac and skeletal myopathy. Many countries have included FAO defects in their expanded neonatal screening programs. The main reason for screening is the life-threatening hypoglycemia that can lead to coma or sudden death, but can be prevented by avoidance of fasting. The treatment opportunities for (cardio)myopathy are suboptimal and new developments are hampered by a lack of fundamental insight into the consequences of a FAO defect. The goal of this research line is to define the pathogenetic mechanisms that underlie the various symptoms of FAO defects and to design rational therapeutic strategies for patients affected with FAO defects.