Stuart L. Schreiber

Research in my laboratory involves the melding of synthetic organic chemistry with cell biology. In these chemical genetic studies, low-molecular-weight, cell-permeable molecules have been synthesized and used to understand and control signal transduction pathways involved in cell cycle regulation. These organic ligands are used to cause either a conditional loss-of-function following binding to the products of wild-type alleles or a gain-of-function following binding to the products of rationally designed conditional alleles. The loss-of-function results from synthetic ligands that bind specifically to the encoded protein, whereas the gain-of-function results from the use of synthetic "dimerizers" that bring two halves of the encoded protein together. Using protein-structure-based combinatorial chemistry, my laboratory has provided an illustration of how chemical genetics can be generalized and extended.