The modern drug discovery target identification paradigm depends on serendipitous observations, careful review of scientific literature, and study of animal models of disease. Problematically, the only tool to validate targets in humans has been clinical trials, which must follow years of preceding drug discovery work, are enormously expensive, and nonetheless fail more than half the time because of lack of efficacy. Although drugs with validated genetic mechanisms are estimated to be twice as likely to succeed in clinical trials as those without such genetic evidence, only about 2% of preclinical stage drugs have mechanisms with direct genetic support. Methods enabling target selection based on genetic evidence, and validation in humans at the outset of the discovery process are desperately needed.
The mission of our group is to identify new therapeutic targets and to do so we are reimagining the drug discovery paradigm. Our primary goals include:
creating computational methods to dissect the genetics of complex diseases and elucidate causal genes
modelling disease using human stem cell-derived neurons, other relevant cell types, and more complex systems such as brain organoids
developing genomic assays enabling genetic target validation at the outset of the drug discovery process
We are also actively collaborating on these goals with faculty from MIT, Harvard, and the Broad Institute, one of whom would be a co-mentor for a postdoc in the group.