研究领域

查看导师新发文章 （温馨提示：请注意重名现象，建议点开原文通过作者单位确认）

The use of small molecule ligands to perturb protein function is a powerful approach to understanding gene function that complements the genetic approach. We are interested in applying a chemical biology approach to three research areas: (I) The first is to dissect and further elucidate the process of eukaryotic protein synthesis. Small molecule ligands, acting as inhibitors, have provided formidable insight into the complexity of prokaryotic translation. We propose that similar inhibitors of eukaryotic translation will be valuable tools to better understand the intricacies and regulation of this pathway. Moreover, only from a more complete picture of eukaryotic protein synthesis can one obtain the necessary means to design therapies that target translation to treat disease. In sum, our research program is aimed at identifying inhibitors of mammalian translation, elucidating their mode of action, and identifying their molecular targets. (II) The increasing awareness of the essential role of RNA in many biological processes and in the progression of disease makes it a very attractive therapeutic target. RNA plays an essential role in many macromolecular processes (sometimes contributing catalytic activity), contains complex secondary and tertiary structural folds, and lacks a cellular repair mechanism. Targeting RNA has also the potential to regulate gene expression in fashions not available by current drug strategy approaches - for example, to achieve allele-specific modulation of gene expression (when allelic sequence differences result in altered RNA conformations) or isoform-specific modulation of gene expression. One of our research efforts is to target specific RNA motifs involved in disease with small molecule ligands to perturb gene expression. (III) We are also interested in better understanding changes in gene expression that occur during the transformation process. We have been characterizing the biochemical properties of a tumor suppressor gene, WT1, a gene that is mutated in Wilms' tumor - a pediatric malignancy of the kidney. As such we have characterized structure/function relationships of WT1, characterized several of its downstream targets, and shown a role for the product of this gene in normal urogenital development. We have also characterized genetic events involved in the progression of this disease. An important aspect of cancer progression is angiogenesis, the growth of new blood vessel to bring nutrients to transformed cells. Current work in the lab is geared towards better understanding the process of angiogenesis in cancer by studies aimed at post-transcriptional regulation of genes involved in this event.