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Research group/lab  |  P.I. W. Edward Visser, MD, PhD

Thyroid laboratory

The Thyroid laboratory (part of the Erasmus MC Academic for Thyroid Diseases) investigates the role of thyroid hormone in health and disease.

About our research group/lab

Our research

Our research team pursues different lines of research that are interconnected with the clinics of the Erasmus MC Academic for Thyroid Diseases.
Thyroid hormone is essential for development and metabolism. At the cellular level, thyroid hormone bioactivity is governed by plasma membrane transporters, deiodinating enzymes and nuclear receptors. Our group has identified several disorders that result from mutations in either of those key players in local thyroid hormone signaling. Employing established and novel technologies, we investigate normal and abnormal thyroid hormone signaling using different models, including patient-derived induced pluripotent stem cells

Thyroid hormone transport

Our group discovered that mutations in the thyroid hormone transporter MCT8 give rise to a severe disease with intellectual and motor disability and abnormal thyroid function tests in the blood. After preclinical development, we coordinated an international trial that showed beneficial effects in such patients who were treated with the thyroid hormone analog Triac. A second international trial is underway. Patient-derived induced pluripotent stem cells are employed to model this disease.

Thyroid hormone receptor

We and others discovered a novel disease due to mutations in the thyroid hormone receptor alpha, which is associated with a variable phenotype of intellectual and motor disability, delayed growth and abnormal thyroid hormone concentrations. Our group focuses on clinical phenotyping of patients with thyroid hormone resistance and on unravelling the molecular mechanisms behind the disease.

Thyroid and pregnancy

Thyroid hormone is essential for a normal development of virtually all tissues, especially the brain. As a consequence, untreated overt maternal hypothyroidism during pregnancy is associated with an adverse risk of pregnancy and fetal outcomes. In recent years our studies on the consequences of mild changes in thyroid function for clinical outcome, as well as the work on re-defining the reference range for thyroid function have altered clinical practice and international guidelines. Current research focuses on a better understanding of gestational physiology, regulation of thyroid hormone transport across the placenta, the consequences of endocrine disruptors on the thyroid system during pregnancy and improving treatment of patients with thyroid disease during pregnancy. This line of research is closely embedded in the Generation R study, a population-based pregnancy cohort. 

Optimal thyroid function and clinical outcome 

Thyroid hormone plays a crucial role in maintenance of tissue function. Altered thyroid function is associated with an increased prevalence of cardiovascular, neurological and other diseases of older age. In addition, a major part of patients with treated thyroid disease continue to have complaints of (tissue-specific) hypothyroidism. Current research focuses on the optimal timing and threshold for treatment of thyroid disease, as well unravelling the genetic and environmental determinants of the thyroid setpoint. This line of research is closely embedded in the Rotterdam Study (ERGO), a population-based cohort in aging individuals.

Our projects

  • New thyroid hormone transporters: We aim to identify the new thyroid hormone transporters and their role in physiology
  • Mechanisms underlying defective thyroid hormone transport: We employ patient-derived cells as ex vivo model to study the underlying mechanisms of disease (collaboration Dept of Molecular Psychiatry)
  • International trial with Triac in MCT8 deficiency: Triac Trial II: We coordinate a multicentre international clinical trial in whom young children are treated with the thyroid hormone analog Triac and investigate the effects on neurocognitive outcomes
  • New thyroid hormone metabolism pathway: We investigate the functional role of AADAT as a new key player in thyroid hormone metabolism
  • Thyroid hormone action in health and disease: We investigate the molecular regulation of thyroid hormone receptors and study the functional consequences of patient-derived mutations in thyroid hormone receptor alpha.
  • Unravelling the mechanisms and regulation of transport of thyroid hormone across the placenta: We aim to identify the relevant thyroid hormone transporters in placenta, and study their role in an ex-vivo placenta perfusion model using specific inhibitors 
  • Unravelling the role of non-classical thyroid hormone metabolites in (patho)fysiology: We have recently developed (in close collaboration with the Dept of Clinical Chemistry) a novel method to measure a full profile of thyroid hormone metabolites in a single run. Current studies focus on the role of these metabolites in health and disease.
  • Unravelling the mechanisms of endocrine disruption on the thyroid system during pregnancy, and its consequences: We aim to study the consequences of several endocrine disruptors on thyroid hormone action as well as pregnancy outcome.

Key Publications

Collaborations

Collaboration within Erasmus MC

  • Department of Clinical Chemistry
  • Department of Molecular Psychiatry
  • Dept of Epidemiology
  • Dept of Child Psychiatry
  • Dept of Pharmacology
  • Dept Of Obstertics and Gynecology
  • Dept of Neurology

Collaboration outside of Erasmus MC

  • The Thyroidomics Consortium
  • The consortium on Thyroid and Pregnancy
  • The Thyroid Studies Collaboration

Funding & Grants

 

Our team

Any questions or comments?

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