- SENIOR FACULTY Genetics and Genomic Sciences
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 at Mount Sinai and will continue his research on fatty acid oxidation defects with the aim to develop new therapeutic options. In collaboration with the Institute for Genomics and Multiscale Biology, 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.
To view a complete list of Dr. Houten's publication click here
Neil Buist Award
Society for Inherited Metabolic Disorders (SIMD)
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, 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.
Houten SM, Kuis W, Duran M, de Koning TJ, van Royen-Kerkhof A, Romeijn GJ, Frenkel J, Dorland L, de Barse MM, Huijbers WA, Rijkers GT, Waterham HR, Wanders RJ, Poll-The BT. Mutations in MVK, encoding mevalonate kinase, cause hyperimmunoglobulinaemia D and periodic fever syndrome. Nature genetics 1999 Jun; 22(2).
Houten SM, Romeijn GJ, Koster J, Gray RG, Darbyshire P, Smit GP, de Klerk JB, Duran M, Gibson KM, Wanders RJ, Waterham HR. Identification and characterization of three novel missense mutations in mevalonate kinase cDNA causing mevalonic aciduria, a disorder of isoprene biosynthesis. Human molecular genetics 1999 Aug; 8(8).
Houten SM, Wanders RJ, Waterham HR. Biochemical and genetic aspects of mevalonate kinase and its deficiency [review]. Biochimica et biophysica acta 2000 Dec; 1529(1-3).
Houten SM, Koster J, Romeijn GJ, Frenkel J, Di Rocco M, Caruso U, Landrieu P, Kelley RI, Kuis W, Poll-The BT, Gibson KM, Wanders RJ, Waterham HR. Organization of the mevalonate kinase (MVK) gene and identification of novel mutations causing mevalonic aciduria and hyperimmunoglobulinaemia D and periodic fever syndrome. European journal of human genetics 2001 Apr; 9(4).
Houten SM, Frenkel J, Rijkers GT, Wanders RJ, Kuis W, Waterham HR. Temperature dependence of mutant mevalonate kinase activity as a pathogenic factor in hyper-IgD and periodic fever syndrome. Human molecular genetics 2002 Dec; 11(25).
Houten SM, Schneiders MS, Wanders RJ, Waterham HR. Regulation of isoprenoid/cholesterol biosynthesis in cells from mevalonate kinase-deficient patients. The Journal of biological chemistry 2003 Feb; 278(8).
Houten SM, van Woerden CS, Wijburg FA, Wanders RJ, Waterham HR. Carrier frequency of the V377I (1129G>A) MVK mutation, associated with Hyper-IgD and periodic fever syndrome, in the Netherlands. European journal of human genetics 2003 Feb; 11(2).
Houten SM, Frenkel J, Waterham HR. Isoprenoid biosynthesis in hereditary periodic fever syndromes and inflammation [review]. Cellular and molecular life sciences : CMLS 2003 Jun; 60(6).
Watanabe M, Houten SM, Wang L, Moschetta A, Mangelsdorf DJ, Heyman RA, Moore DD, Auwerx J. Bile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP-1c. The Journal of clinical investigation 2004 May; 113(10).
Watanabe M, Houten SM, Mataki C, Christoffolete MA, Kim BW, Sato H, Messaddeq N, Harney JW, Ezaki O, Kodama T, Schoonjans K, Bianco AC, Auwerx J. Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation. Nature 2006 Jan; 439(7075).
Houten SM, Watanabe M, Auwerx J. Endocrine functions of bile acids [review]. The EMBO journal 2006 Apr; 25(7).
Houten SM. Homing in on bile acid physiology. Cell metabolism 2006 Dec 4(6).
Houten SM, Volle DH, Cummins CL, Mangelsdorf DJ, Auwerx J. In vivo imaging of farnesoid X receptor activity reveals the ileum as the primary bile acid signaling tissue. Molecular endocrinology 2007 Jun; 21(6).
Chegary M, te Brinke H, Doolaard M, IJlst L, Wijburg FA, Wanders RJ, Houten SM. Characterization of L-aminocarnitine, an inhibitor of fatty acid oxidation. Molecular genetics and metabolism 2008 Apr; 93(4).
Houten SM. Metabolomics: unraveling the chemical individuality of common human diseases [review]. Annals of medicine 2009; 41(6).
Houten SM, Chegary M, te Brinke H, Wijnen WJ, Glatz JF, Luiken JJ, Wijburg FA, Wanders RJ. Pyruvate dehydrogenase kinase 4 expression is synergistically induced by AMP-activated protein kinase and fatty acids. Cellular and molecular life sciences 2009 Apr; 66(7).
Chegary M, te Brinke H, Ruiter JP, Wijburg FA, Stoll MS, Minkler PE, van Weeghel M, Schulz H, Hoppel CL, Wanders RJ, Houten SM. Mitochondrial long chain fatty acid beta-oxidation in man and mouse. Biochimica et biophysica acta 2009 Aug; 1791(8).
Houten SM, Wanders RJ. A general introduction to the biochemistry of mitochondrial fatty acid β-oxidation [review]. Journal of inherited metabolic disease 2010 Oct; 33(5).
Wanders RJ, Ruiter JP, IJLst L, Waterham HR, Houten SM. The enzymology of mitochondrial fatty acid beta-oxidation and its application to follow-up analysis of positive neonatal screening results [review]. Journal of inherited metabolic disease 2010 Oct; 33(5).
Nouws J, Nijtmans L, Houten SM, van den Brand M, Huynen M, Venselaar H, Hoefs S, Gloerich J, Kronick J, Hutchin T, Willems P, Rodenburg R, Wanders R, van den Heuvel L, Smeitink J, Vogel RO. Acyl-CoA dehydrogenase 9 is required for the biogenesis of oxidative phosphorylation complex I. Cell metabolism 2010 Sep; 12(3).
Bakermans AJ, Geraedts TR, van Weeghel M, Denis S, João Ferraz M, Aerts JM, Aten J, Nicolay K, Houten SM, Prompers JJ. Fasting-induced myocardial lipid accumulation in long-chain acyl-CoA dehydrogenase knockout mice is accompanied by impaired left ventricular function. Circulation. Cardiovascular imaging 2011 Sep; 4(5).
Stobbe MD, Houten SM, Jansen GA, van Kampen AH, Moerland PD. Critical assessment of human metabolic pathway databases: a stepping stone for future integration. BMC systems biology 2011; 5.
Houten SM, Argmann CA. New driver for lipid synthesis. Cell 2011 Nov 147(4).
Soeters MR, Serlie MJ, Sauerwein HP, Duran M, Ruiter JP, Kulik W, Ackermans MT, Minkler PE, Hoppel CL, Wanders RJ, Houten SM. Characterization of D-3-hydroxybutyrylcarnitine (ketocarnitine): an identified ketosis-induced metabolite. Metabolism: clinical and experimental 2012 Jul; 61(7).
Houten SM, Denis S, Argmann CA, Jia Y, Ferdinandusse S, Reddy JK, Wanders RJ. Peroxisomal L-bifunctional enzyme (Ehhadh) is essential for the production of medium-chain dicarboxylic acids. Journal of lipid research 2012 Jul; 53(7).
Stobbe MD, Houten SM, van Kampen AH, Wanders RJ, Moerland PD. Improving the description of metabolic networks: the TCA cycle as example. FASEB journal 2012 Sep; 26(9).
van Weeghel M, te Brinke H, van Lenthe H, Kulik W, Minkler PE, Stoll MS, Sass JO, Janssen U, Stoffel W, Schwab KO, Wanders RJ, Hoppel CL, Houten SM. Functional redundancy of mitochondrial enoyl-CoA isomerases in the oxidation of unsaturated fatty acids. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2012 Oct; 26(10).
Schooneman MG, Vaz FM, Houten SM, Soeters MR. Acylcarnitines: reflecting or inflicting insulin resistance? [review]. Diabetes 2013 Jan; 62(1).
Violante S, IJlst L, te Brinke H, Tavares de Almeida I, Wanders RJ, Ventura FV, Houten SM. Carnitine palmitoyltransferase 2 and carnitine/acylcarnitine translocase are involved in the mitochondrial synthesis and export of acylcarnitines. FASEB journal 2013 May; 27(5).
Bakermans AJ, van Weeghel M, Denis S, Nicolay K, Prompers JJ, Houten SM. Carnitine supplementation attenuates myocardial lipid accumulation in long-chain acyl-CoA dehydrogenase knockout mice. Journal of inherited metabolic disease 2013 Apr; 36(6).
Houten SM, te Brinke H, Denis S, Ruiter JP, Knegt AC, de Klerk JB, Augoustides-Savvopoulou P, Häberle J, Baumgartner MR, Coşkun T, Zschocke J, Sass JO, Poll-The BT, Wanders RJ, Duran M. Genetic basis of hyperlysinemia. Orphanet journal of rare diseases 2013 Apr; 8.
Houten SM, Herrema H, te Brinke H, Denis S, Ruiter JP, van Dijk TH, Argmann CA, Ottenhoff R, Müller M, Groen AK, Kuipers F, Reijngoud DJ, Wanders RJ. Impaired amino acid metabolism contributes to fasting-induced hypoglycemia in fatty acid oxidation defects. Human molecular genetics 2013 Aug;.
Bakermans AJ, Dodd MS, Nicolay K, Prompers JJ, Tyler DJ, Houten SM. Myocardial energy shortage and unmet anaplerotic needs in the fasted long-chain acyl-CoA dehydrogenase knockout mouse. Cardiovascular research 2013 Oct;.
Nouws J, te Brinke H, Nijtmans LG, Houten SM. ACAD9, a complex I assembly factor with a moonlighting function in fatty acid oxidation deficiencies. Human molecular genetics 2013 Oct;.
Houten SM, Denis S, te Brinke H, Jongejan A, van Kampen AH, Bradley EJ, Baas F, Hennekam RC, Millington DS, Young SP, Frazier DM, Gucsavas-Calikoglu M, Wanders RJ. Mitochondrial NADP(H) deficiency due to a mutation in NADK2 causes dienoyl-CoA reductase deficiency with hyperlysinemia. Human molecular genetics 2014 Sep; 23(18).
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Dr. Houten has not yet completed reporting of Industry relationships.
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