Carson C. Thoreen
Mapped how mTORC1 controls translation of the growth machinery
Postdoc, Whitehead Institute/MIT (Sabatini lab) · Associate Professor of Cellular & Molecular Physiology, Yale School of Medicine
Carson Thoreen trained as a postdoc in David Sabatini's lab, where he helped develop an ATP-competitive mTOR inhibitor (PP242) that, unlike rapamycin, fully blocks mTORC1 activity — revealing a whole set of rapamycin-resistant functions, especially in translation, that classic rapamycin treatment had been missing.
Building on that tool, Thoreen mapped how mTORC1 controls protein synthesis at the molecular level, proposing a unifying model in which mTORC1 phosphorylates 4E-BP proteins to release the translation initiation factor eIF4E, selectively boosting translation of mRNAs needed for cell growth. He now runs his own lab at Yale, studying how mTOR-dependent translation is wired at the level of individual mRNA sequences.
The timeline below follows Thoreen's contributions gathered in this Atlas.
Milestones in the Atlas
| Year | Evidence | Study |
|---|---|---|
| 2006 | M | Ablation in mice of the mTORC components raptor, rictor, or mLST8 reveals that mTORC2 is required for signaling to Akt-FOXO and PKCalpha, but not S6K1 GUE2006 The foundational genetic 'dissection' of the two complexes in living mice. Deleting Raptor was lethal early (mTORC1 essential); deleting Rictor or mLST8 selectively knocked out mTORC2 signaling to Akt and PKCalpha but spared S6K1. This cleanly assigned jobs to each complex and showed mLST8 is an mTORC2-specific requirement in mice. |
| 2007 | M | PRAS40 is an insulin-regulated inhibitor of the mTORC1 protein kinase SAN2007 Identified PRAS40 as the missing insulin-controlled brake INSIDE mTORC1. When insulin is absent PRAS40 clamps the complex shut; insulin makes Akt phosphorylate PRAS40, releasing the brake so Rheb can fully switch mTORC1 on. Explained how hormone signals set the exact strength of mTORC1 activity. |
| 2009 | M | An ATP-competitive mammalian target of rapamycin inhibitor reveals rapamycin-resistant functions of mTORC1 THO2009 Develops an ATP-competitive mTOR inhibitor that reveals rapamycin-resistant functions of mTORC1. |
| 2009 | M | DEPTOR is an mTOR inhibitor frequently overexpressed in multiple myeloma cells and required for their survival PET2009 Identified DEPTOR as a built-in brake on BOTH mTOR complexes. The twist: in some multiple myelomas DEPTOR is overexpressed, which by relieving a feedback loop actually keeps pro-survival Akt signaling ON - a neat example of how an 'inhibitor' can be co-opted by cancer. |
| 2012 | M | A unifying model for mTORC1-mediated regulation of mRNA translation THO2012 Proposes a unifying model for how mTORC1 controls mRNA translation through 4E-BP and eIF4E. |