The Salas-Lucia laboratory integrates neurobiology and endocrinology to investigate how thyroid hormones mediate their action during brain development. We are paying special attention to the biology of the neural precursor cells and microglia while exploring the processes of neurogenesis. To do so, we combine different perspectives, including bioenergetics, epigenetics, molecular and cell biology, and biochemistry.

We study cellular mechanisms that can customize thyroid hormone action in the human brain. These mechanisms involve four components: the thyroid hormone cell membrane monocarboxylate transporter 8 (MCT8), the type 2 and type 3 deiodinase (DIO2 and DIO3), and the nuclear receptors (TRs). These components work together to rapidly enhance/reduce hormone action by regulating the amounts of locally available thyroid hormones in neural cells.

We are currently investigating how thyroid hormone regulates bioenergetic processes that support neurogenesis during the development of the cerebral cortex. We are particularly interested in how thyroid hormone influences mitochondrial function and energy metabolism in neural progenitor cells. At the same time, we study how epigenetic mechanisms—such as DNA methylation and histone modifications—modulate thyroid hormone signaling. We focus on the imprinted genes involved in this pathway and explore how parental origin influences their expression and, in turn, the developmental roles of thyroid hormones during cerebral cortex development.

To explore these questions, we use cutting-edge models derived from human induced pluripotent stem cells (iPSCs), including cerebral organoids and differentiated neurons. These systems allow us to model early brain development in a dish. We combine transcriptomics, advanced imaging, and biochemical techniques to uncover how thyroid hormone shapes neural development at the molecular and cellular levels.