Drug Discovery

    Over the past two decades, tremendous efforts have been made to develop drugs capable of modulating today's most debilitating and costly diseases. However, despite the recent advances offered by genome sequences, the rate of new drug discovery has decreased and costs have gone up. Much of this can be attributed to the simplicity of drug discovery assays, and subsequent attrition due to unforeseen defects and side- effects. An obvious, although difficult solution, would be to develop high throughput drug screens that could be conducted using live animals.

    To this end, we have developed a high throughput zebrafish system that allows the visualization and isolation of active drug candidates in live fish (Tiefenbach et al, 2010). We have generated 48 transgenic zebrafish lines, one representing each of the 48 human nuclear receptors, which are one of the most important and successful families of drug target proteins. A couple of screens have already been conducted with tremendous success. One of our discoveries, a drug that is already FDA approved for other indications, looks to have excellent potential for metabolic syndrome diseases such as diabetes.