Research interest

Selenium is an essential trace element, which exerts a variety of health benefits. The nutritional requirement for this micronutrient is due to its function in the selenoproteins, whose synthesis is reduced when dietary selenium becomes limiting. The 25 human selenoproteins play important roles in anti-oxidant defense, thyroid hormone metabolism, fertility, immunity, and development. Selenium is incorporated into selenoproteins as Selenocysteine (Sec), the 21^st amino acid. The translation of selenoprotein mRNAs poses a serious challenge to the cell because Sec is encoded by UGA, which is normally read as a stop codon. Our long-term goal is to understand how UGA is recoded as Sec and how this pathway is regulated in selenium deficiency. We identified proteins that are important components of the UGA recoding machinery, including SECIS-binding protein 2 (SBP2) and ribosomal protein L30. Importantly, defects in the SBP2:SECIS interaction have been linked to human disease. Thus fully elucidating the Sec incorporation pathway is an important translational goal. We are also interested in how the expression of the selenoproteome is regulated during selenium insufficiency, an important health problem in many regions of the world. When selenium becomes limiting, there is a hierarchy of expression, in which certain essential selenoproteins are synthesized at the expense of others. We demonstrated that this hierarchy is dictated by eukaryotic initiation factor 4a3 (eIF4a3) and nucleolin, which selectively regulate selenoprotein mRNA translation. We are currently characterizing novel proteins, which regulate selenoprotein expression in a transcript-selective or tissue-specific manner.