Thyroid hormones and their receptors: how they work and what they do 

Our group investigates the diverse actions of thyroid hormones (TH) and their receptors (TRs) α and β, with the goal of understanding the mechanisms of TH action and translating these insights into therapeutic strategies.

Thyroid hormone receptors act as key regulators of cellular physiology. We explore their classical nuclear functions—how ligand-bound receptors interact with DNA, recruit cofactors, and modulate gene expression programs that shape cellular metabolism and identity. In parallel, we investigate noncanonical, extranuclear signaling pathways in which TRs initiate rapid cytosolic signaling events. By integrating molecular, genomic, and biochemical approaches, we seek to define how both nuclear and noncanonical modes of action contribute to normal physiology and disease progression.

One major research area focuses on G-quadruplex (G4) structures within the THRA gene. These non-canonical nucleic acid conformations play increasingly recognized roles in transcriptional regulation and RNA processing. We examine how G-quadruplexes influence alternative splicing of TRα1 and TRα2, regulate TRα protein expression, and potentially serve as novel control points of TRα action. Because G-quadruplexes are emerging as attractive targets for small-molecule therapeutics, our work also explores their relevance as druggable elements capable of modulating TRα-mediated pathways in a selective and tissue-specific manner.

Another major focus is the therapeutic application of thyroid hormones and the targeted manipulation of thyroid hormone action. We study how thyroid hormone signaling shapes the course and outcome of diseases across multiple organ systems, with specific attention to the role of TR isoforms in mediating beneficial or maladaptive effects. This includes investigating the phenotype of resistance to thyroid hormone α and β.

Our disease models include hepatic steatosis, white adipose tissue dysfunction, alcoholic liver disease, malignant melanoma and pulmonary infections. In inflammatory diseases, we study T-cell–mediated immunity with a focus on regulatory T-cell biology. Through TR α and β knockout and knock in models, we aim to uncover how thyroid hormone pathways influence inflammation and metabolism, and how targeted activation or inhibition of TR signaling may improve disease outcomes.

Together, these research topics form a unified effort to understand thyroid hormone effects from TR expression, TR structure and signaling to their role in (patho)physiology. By combining mechanistic studies with translational goals, we seek new therapeutic approaches for endocrine, metabolic, hepatic, and immune-related diseases driven by altered thyroid hormone (receptor) action.