Role of the enigmatic TR2 isoform in regulating cardiac TH function (P11)

• Subject Area: Human Genetics
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 424957847

Thyroid hormone (TH) action in the heart is predominantly controlled by its receptor TR alpha. While we have shown that its isoforms TR alpha1 and TR alpha2 can form dimers, the functional relevance of TR alpha2 is still unsolved. During the differentiation of hiPSCs into cardiomyocytes (and also neuronal cells) we identified a shift from TR alpha1 to TR alpha2 expression. Our project now aims to delineate TR alpha2’s role during cardiomyocytes’ maturation and function. To this end we will characterize selected and functionally validated THRA variants in fusion-tagged THRA hiPSCs under cardiomyocyte (and neuronal) differentiation and will combine genome-wide analyses of TR alpha1/2-DNA binding, epigenetic alteration, and expression studies together with functional analyses.

• DFG Programme: CRC/Transregios
• Subproject of: TRR 296: Local control of TH action (LocoTact)
• Applicant Institution: Universität Duisburg-Essen
• Project Heads: Professor Dr. Frank Kaiser; Professor Dr. Johannes Köster