PhD defence W. (Wenjun) Liao

Below is a brief summary of the dissertation:

Thyroid hormones control human growth, development and metabolism. Their levels are tightly balanced in the body, and they work by attaching to thyroid hormone receptors inside cells. When these receptors are changed by genetic mutations, tissues stop responding properly to thyroid hormones. This condition is called Resistance to Thyroid Hormone (RTH). Two main forms exist: RTHα and RTHβ, each causing different clinical symptoms.

This thesis explores diagnosis, underlying molecular mechanisms and treatment options for RTH. It describes real patient cases, including one severely‑affected RTHβ patient whose mosaic mutation delayed diagnosis, and another patient initially misdiagnosed with a pituitary tumour. This work also studies TRIAC, a thyroid‑hormone‑like drug used to treat RTHβ. Using patient data, cell experiments and zebrafish models, we show TRIAC can work in several different ways: it may activate normal receptors, or directly act on certain mutated receptors.

We further investigate an RTHα family with short stature linked to the H175R receptor variant. Our results confirm that persistent binding of inhibitory proteins to mutated receptors, even with thyroid hormone present, drives typical RTHα disease features. This research improves our understanding of RTH and supports better clinical recognition and treatment for affected patients.