Chemical Biology
The Chemical Biology program within the Stanley Center is focused on both cell-based screens in various neuronal and non neuronal cells as well as in vitro biochemical assays. The cell screens are aimed at defining a cell state that is thought to be related to a pathophysiological process involved in bipolar disorder or schizophrenia. High-throughput screens are being conducted that can potentially detect compounds that will confer a more desirable state or biochemical activity. Secondary screens are used to further characterize initial hits.
A disparate set of technologies are employed: imaging-based methods measure neurite outgrowth, protein localization, or reporter gene activation in the presence of a small molecule or an RNAi; gene expression methods measure increase or decrease in expression of ‘signature genes’; small-molecule microarrays identify specific compounds that bind a desired target. Follow-up studies to identify the mechanism of action or the target in cell-based assays are being carried out; biochemical assays are also developed to support rapid characterization of hits; and follow-up chemistry is being done, with iterations of screening, to identify novel molecules with the most desirable properties. The goal of the Stanley Center Chemical Biology program is to identify new mechanisms that might lead to new treatments for psychiatric illnesses.
Currently there are three main projects: lithium signaling, HDACs (chromatin remodeling), and neurotrophic factors. As risk-associated genes emerge from the genetic analyses, new chemical biology projects will be initiated based on these genetically-validated targets or pathways. Overall, our challenge is to constantly guide Stanley Center research toward the pathways and targets deemed most disease- and therapeutically-relevant. Projects not meeting these criteria but having valuable basic research applications may be pursued in our researchers’ academic labs.