Discoveries at the interface of pathways, phenotypic screening, and chemical biology

In situations where the genetic bases of diseases are established and the biology is amenable to intervention, we can often develop a therapy. More frequently, understanding the genetics of disease does not yield a specific target and instead points us at specific signaling pathways and processes that are misregulated. For these situations, we have brought the expertise and technologies of several scientific disciplines to bear on the challenge of identifying new targets and mechanisms as potential therapies. A particular area of attention is small molecule phenotypic screening as an approach towards discovering new targets, new mechanisms, and new therapies. We will describe several of our technologies and how we applied them to particular aspects of disease biology. We will also share several examples where our research has uncovered new targets and new mechanisms that may be amenable for therapies.