Erik Schoenmakers

We have shown how defects in SECISBP2, essential for synthesis of selenocysteine-containing proteins, causes a multisystem disease encompassing male infertility, muscular dystrophy, aneurysmal aortic dilatation, elevated cellular ROS & tissue oxidative damage and disordered thyroid hormone metabolism. Longterm sequelae (eg cancer risk, accelerated ageing) oxidative stress remain to be elucidated. We identified a genetic defect in tRNA-SEC, in which posttranslational tRNA modification selectively preserves synthesis of essential, housekeeping but not stress-induced selenoproteins. We have identified dominant negative inhibition by defective nuclear hormone receptors in patients as a common molecular mechanism in Resistance to Thyroid Hormone α and β and in PPARγ-mediated insulin resistance.