Schreiber and Crabtree demonstrated that small molecules could activate a signaling pathway in an animal with temporal and spatial control. Dimerizer kits have been distributed freely resulting in many peer-reviewed publications. Its promise in gene therapy has been highlighted by the ability of a small molecule to activate a small-molecule regulated EPO receptor and to induce erythropoiesis (Ariad Pharmaceuticals, Inc.), and more recently in human clinical trials for treatment of graft-vs-host disease. In 1994, Schreiber and co-workers investigated (independently with David Sabitini) the master regulator of nutrient sensing, mTOR. They found that the small molecule rapamycin simultaneously binds FKBP12 and mTOR (originally named FKBP12-rapamycin binding protein, FRAP). Using diversity-oriented synthesis and small-molecule screening, Schreiber illuminate the nutrient-response signaling network involving TOR proteins in yeast and mTOR in mammalian cells. Small molecules such as uretupamine and rapamycin were shown to be particularly effective in revealing the ability of proteins such as mTOR, Tor1p, Tor2p, and Ure2p to receive multiple inputs and to process them appropriately towards multiple outputs (in analogy to multi-channel processors). Several pharmaceutical companies are now targeting the nutrient-signaling network for the treatment of several forms of cancer, including solid tumors. In 1995, Schreiber and co-workers found that the small molecule lactacystin binds and inhibits specific catalytic subunits of the proteasome, a protein complex responsible for the bulk of proteolysis in the cell, as well as proteolytic activation of certain protein substrates. As a non-peptidic proteasome inhibitor lactacysin has proven useful in the study of proteasome function. Lactacystin modifies the amino-terminal threonine of specific proteasome subunits. This work helped to establish the proteasome as a mechanistically novel class of protease: an amino-terminal threonine protease. The work led to the use of bortezomib to treat multiple myeloma. In 1996, Schreiber and co-workers used the small molecules trapoxin and depudecin to investigate the histone deacetylases (HDACs). Prior to Schreiber's work in this area, the HDAC proteins had not been isolated. Coincident with the HDAC work, David Allis and colleagues reported work on the histone acetyltransferases (HATs).