Universite Libre de Bruxelles - IRIBHM

The function of the thyroid gland is to capture iodide to synthesize hormones that act on almost all tissues and are essential for normal growth and metabolism. Low plasma levels of thyroid hormones lead to hypothyroidism which is one of the most common diseases in humans. The aim of the proposed project is to use human thyroid organoids for modelling rare unexplained pathological situations leading to hypothyroidism. We will focus on congenital hypothyroidism with dysgenesis (CHTD) and TSH resistance syndrome (RTSH). 

We will take advantage of: 

1) our knowhow in generating functional human thyroid organoids from pluripotent stem cells.

2) the availability of fibroblasts from monozygotic twins discordant for CHTD.

3) the identification of a genetic defect in a non-coding region of Chr15 in patients with RTSH. 

The goal is to model these two rare thyroid pathologies to identify the underlying molecular mechanisms by generating thyroid organoids either from IPSc (CHTD-TWINS) or after genome editing of the stem cell line used in the laboratory (RTSH syndrome). The translation of identified or unidentified genetic/epigenetic abnormalities from patients with congenital thyroid disease into experimentally validated models of pathogenic mechanisms will be a central paradigm of this project strategy.