Thyroid-hormone regulated gene expression in cardiac and skeletal muscle.
Warner Simonides studied Biochemistry at the State University Leiden, The Netherlands and obtained his Ph.D. with honors in 1985 for studies which identified a mechanism of skeletal-muscle contractile dysfunction in thyroid disease. He continued this research line as researcher at the Department of Physiology of the Free University, Amsterdam, which included a period at the Thyroid Division of the Brigham and Women’s Hospital, Harvard Medical School (1991-1993), where he identified one of the molecular mechanisms of thyroid-hormone action in muscle. He was appointed assistant professor (1999) and associate professor (2006) at the Department of Physiology of the VU University Medical Center, Amsterdam and the research line now also included cardiac action of thyroid hormone. He is co-founder and chairman of the Dutch Thyroid Research Foundation.
Funded by The Dutch Heart Foundation, ZonMW and the VUmc, altered cardiac metabolism of thyroid hormone was identified as a contributing factor in the development of heart failure in rat and mouse models of pulmonary hypertension and myocardial infarction. The principal focus of current research is on determining the molecular mechanisms and clinical relevance of cardiac-specific metabolism of thyroid hormone in chronic heart failure.
Selection of recent publications
Janssen R, Zuidwijk MJ, Muller A, van Mil A, Dirkx E, Oudejans CBM, Paulus WJ, Simonides WS. MicroRNA 214 is a potential regulator of thyroid hormone levels in the mouse heart following myocardial infarction, by targeting the thyroid-hormone inactivating enzyme deiodinase type III. Front Endocrinol. Vol 7, doi: 10.3389/fendo.2016.00022, 2016
Salvatore D, Simonides WS, Dentice M, Zavacki AM, Larsen PR.Thyroid hormones and skeletal muscle-new insights and potential implications. Nature Rev Endocrinol 10, 206-214, 2014.
Janssen R, Zuidwijk MJ, Muller A, Mulders J, Oudejans CBM, Simonides WS. Cardiac expression of deiodinase type 3 (Dio3) following myocardial infarction is associated with the induction of a pluripotency microRNA signature from the Dlk1-Dio3 genomic region. Endocrinology 154, 1973-1978, 2013.
Pol CJ, Muller A, Zuidwijk MJ, van Deel ED, Kaptein E, Saba A, Marchini M, Zucchi R, Visser TJ, Paulus WJ, Duncker DJ, Simonides WS. Left-ventricular remodeling following myocardial infarction is associated with a cardiomyocyte-specific hypothyroid condition. Endocrinology 152, 669-679, 2011.
Redout EM, van der Toorn A, Zuidwijk MJ, van Beek-Harmsen BJ, van de Kolk CWA,
van Echteld CJA, Musters RJP, van Hardeveld C, Paulus WJ, Simonides WS. Antioxidant treatment attenuates pulmonary arterial hypertension-induced heart failure. Am J Physiol Heart Circ Physiol 298, H1038-H1047, 2010.
Simonides WS, Mulcahey MA, Redout EM, Muller A, Zuidwijk MJ, Visser TJ, Wassen FWJS, Crescenzi A, da-Silva WS, Harney J, Engel FB, Obregon MJ, Larsen PR, Bianco AC, Huang SA. Hypoxia-inducible factor induces local thyroid hormone inactivation in hypoxic-ischemic disease in rats. J Clin Invest 118: 975-983, 2008.
Ongoing research projects
Cardiac-specific activation of type III deiodinase following myocardial infarction: a therapeutic target?
The role of differential expression of deiodinases in skeletal muscle development and disease.