Sander Houten, PhD
- ASSOCIATE PROFESSOR | Genetics and Genomic Sciences
Research Topics:Biochemistry, Enzymology, Genetics, Metabolism, Mitochondria
Dr. Sander M. Houten has a Ph.D. from the faculty of Medicine of the University of Amsterdam. During his PhD project, he discovered that a deficiency of mevalonate kinase causes hyper-IgD syndrome, one of the periodic fever syndromes. He conducted studies to understand the consequences of this defect on cellular isoprenoid and cholesterol metabolism. As a postdoctoral fellow with Dr. Johan Auwerx at the Institut de Génétique et de Biologie Moléculaire et Cellulaire in Strasbourg, France, Dr. Houten studied mechanisms underlying the transcriptional control of metabolism in different mouse models. His research focused on signaling events elicited by metabolites and nuclear hormone receptors. He characterized metabolic effects of bile acids and defined a novel bile acid signaling pathway that affects energy homeostasis. For his second postdoctoral fellowship, Dr. Houten returned to the Academic Medical Center of the University of Amsterdam and combined his interest in regulation of metabolic processes and human genetics. He initiated a line of research on the pathophysiology of mitochondrial fatty acid oxidation defects and was promoted to Principal Investigator. He applied state-of-the-art phenotyping methods to mouse models for mitochondrial fatty acid oxidation defects, which yielded new and unexpected insights in the pathophysiology of hypoglycemia and cardiac hypertrophy associated with these disorders. Dr. Houten is currently a tenured Associate Professor (Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai). He explores pathophysiological mechanisms in disorders of fatty acid oxidation and lysine degradation with the ultimate aim to develop new therapies.
To view a complete list of Dr. Houten's publication click here
Multi-Disciplinary Training AreaGenetics and Data Science [GDS]
MSc, University of Amsterdam
PhD, University of Amsterdam
Science Award: Dutch Society for Clinical Chemistry
SSIEM Award: Society for the Study of Inborn Errors of Metabolism
Founders' Award (Neil Buist Award): Society for Inherited Metabolic Disorders
Wadman – Van Gennip Award: Dutch Society for the Study of Inborn Errors of Metabolism
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, we propose that there is no clear distinction between simple Mendelian disorders and complex diseases, but rather a spectrum of disease phenotypes representing a continuum of diminishing effects from a single gene defect influenced by modifier genes to increasingly shared influence by variants in 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 experimental model systems ‘designed’ for complex diseases to inborn errors of metabolism. Our research demonstrates that by employing this method, we can advance our understanding of inborn errors of metabolism by revealing the molecular networks underlying inborn error disease biology.
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.
Glutaric Aciduria Type 1
Glutaric aciduria type 1 (GA1) is an autosomal recessive inborn error of lysine degradation. Patients can present with brain atrophy and macrocephaly and may develop dystonia after acute encephalopathic crises that lead to striatal degeneration. These crises typically occur in the first year of life and are often triggered by a catabolic state such as those that occur during childhood illnesses. GA1 is caused by a defect of glutaryl-CoA dehydrogenase (GCDH) leading to the accumulation of glutaryl-CoA, glutaric acid and 3-hydroxyglutaric acid, which is thought to be neurotoxic. GA1 is rare (~1 in 100,000), but occurs frequently in some communities and ethnic groups such as the Amish, Ojibwe and Lumbee Indigenous peoples, and black South Africans. GA1 patients benefit from early intervention and the disorder is therefore included in newborn screening programs in many countries including the US. The goal of this research line is to improve current treatment by developing substrate reduction therapy.