Glucocorticoids are the most frequently prescribed medicine today and they are indispensable in the treatment of asthma, inflammation, and cancer. However, two concerns regarding glucocorticoid use remain unresolved. One is that high-dose or long-term glucocorticoids result in troublesome side effects such as metabolic syndrome and osteoporosis; the other is that some patients do not respond to glucocorticoids. We tackle both questions by examining the glucocorticoid receptor.
Translational isoforms of glucocorticoid receptors were recently discovered in our lab and they provide insights into the mechanisms of action of glucocorticoids. Ribosomal shunting and leaky scanning processes generate translational glucocorticoid receptor isoforms. These receptor isoforms have distinct cell-killing and cytokine-suppression capabilities in a bone cancer cell model system. Currently, we are identifying and characterizing the receptor isoforms in different populations of immune cells in diseases such as asthma and cancer. This line of research has implications in several other fields in addition to immunology and oncology. For instance, our findings in glucocorticoid receptor biology have significant impact on research in endocrinology as well.
Publications:
Lu NZ and Cidlowski JA: Translational regulatory mechanisms generate N-terminal glucocorticoid receptor isoforms with unique transcriptional target genes. Mol Cell. 2005 Apr;18(3):331-42.
Lu NZ and Cidlowski JA: Glucocorticoid receptor isoforms generate transcription specificity in cells and tissues. Trends Cell Biol. 2006 Jun;16(6):301-7.
Lu NZ, Collins JB, Grissom SF and Cidlowski JA: Selective regulation of bone cell apoptosis by translational isoforms of the glucocorticoid receptor. Mol Cell Biol. 2007 Aug 6; [Epub ahead of print]"
