Key advances include the discovery that small molecules can function as “molecular glues” that promote protein–protein interactions, the co-discovery of mTOR and its role in nutrient-response signaling, the discovery of histone deacetylases and (with Michael Grunstein and David Allis) the demonstration that chromatin marks regulate gene expression, the development and application of diversity-oriented synthesis to microbial therapeutics, and the discovery of vulnerabilities of cancer cells linked to genetic, lineage and cell-state features, including ferroptotic vulnerabilities.

From the ages of one to four he lived with his family in Villennes-sur-Seine, a small village in France, where his father was a battalion commander at Supreme Headquarters Allied Powers Europe.

[6] Shortly after returning to New Jersey, they moved to Fairfax, VA, where Tom Schreiber worked as an applied mathematician and physicist at Signal Corp on Fort Monmouth.

Notable accomplishments include the total syntheses of complex natural products such as periplanone B, talaromycin B, asteltoxin, avenaciolide, gloeosporone, hikizimicin, mycoticin A, epoxydictymene[10] and the immunosuppressant FK-506.

[citation needed] Following his work on the FK506-binding protein FKBP12 in 1988, Schreiber reported that the small molecules FK506 and cyclosporin inhibit the activity of the phosphatase calcineurin by forming the ternary complexes FKBP12-FK506-calcineurin and cyclophilin-ciclosporin-calcineurin.

Schreiber and Crabtree demonstrated that small molecules could activate a signaling pathway in an animal with temporal and spatial control.

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.

[17] Using diversity-oriented synthesis and small-molecule screening, Schreiber illuminated the nutrient-response signaling network involving TOR proteins in yeast and mTOR in mammalian cells.

[citation needed] In 1996, Schreiber and co-workers used the small molecules trapoxin and depudecin to investigate the histone deacetylases (HDACs).

[citation needed] Schreiber applied small molecules to biology through the development of diversity-oriented synthesis (DOS),[23] chemical genetics,[24] and ChemBank.

[29] Using diversity-oriented synthesis, the Schreiber Lab and collaborators discovered numerous novel antimicrobial compounds including the bicyclic azetidine BRD7929 that could both cure and prevent the transmission of malaria in mice, targeting multiple steps in the life cycle of Plasmodium falciparum.

the Schreiber Lab discovered that when certain aggressive cancer cells become resistant to drug treatments, they also become vulnerable to ferroptosis—a natural cellular self-destruction mechanism triggered by peroxide and iron ions undergoing the Fenton reaction.