Stuart L. Schreiber

Co-discovered mTOR by purifying it as the mammalian target of the FKBP12–rapamycin complex

BA in chemistry, University of Virginia · PhD, Harvard University (Robert B. Woodward, then Yoshito Kishi) · assistant professor, Yale University (1980) · Morris Loeb Professor of Chemistry and Chemical Biology, Harvard University (1988–present, now Emeritus) · co-founder of the Broad Institute · HHMI Investigator (Emeritus) · now Chief Scientific Officer, Arena BioWorks (since 2025)

Faculty profile, Harvard University ↗

In 1994, Schreiber's lab purified the mammalian protein that binds the immunosuppressant complex FKBP12–rapamycin — naming it FRAP, later renamed mTOR — and showed it was the human homolog of yeast TOR1/TOR2, the genes originally implicated in rapamycin's growth-arresting effects. Two years later, his group solved the crystal structure of FKBP12–rapamycin bound to mTOR's FRB domain, revealing the atomic mechanism: a single rapamycin molecule sits in the interface and plugs into two separate hydrophobic pockets, one on FKBP12 and one on FRB, physically gluing the two proteins together. That structure became a founding example of a 'molecular glue' — a small molecule that works not by blocking a single active site but by forcing two proteins into an unnatural complex, a concept that now underlies an entire class of drugs (including PROTACs).

Schreiber trained in organic synthesis at Harvard, first under Robert B. Woodward and then Yoshito Kishi after Woodward's death, before starting his own lab at Yale in 1980 and returning to Harvard in 1988. Through the 1990s he helped found the field of chemical biology, developing diversity-oriented synthesis — methods for building large, structurally diverse small-molecule collections — as a way to probe biology the way genetics probes it with mutations. In 1997 he became founding director of Harvard's Institute of Chemistry and Cell Biology, whose screening infrastructure and chemical-genetics philosophy fed directly into the 2004 founding of the Broad Institute, where he built and led its Chemical Biology Program.

Schreiber is a Howard Hughes Medical Institute Investigator (now Emeritus) and a member of the National Academy of Sciences, the National Academy of Medicine, and the American Academy of Arts and Sciences; he has received the Wolf Prize in Chemistry, among other honors. In 2024 he co-founded Arena BioWorks, a privately funded, non-profit biomedical research institute in Cambridge, MA, where he now serves as Chief Scientific Officer.

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