Rachel L. Wolfson
Identified Sestrin2 as the direct leucine sensor for mTORC1
MD-PhD, Sabatini lab, Whitehead Institute/MIT · Assistant Professor of Cell Biology, Harvard Medical School
Wolfson Lab, Harvard Medical School ↗
Portrait: Harvard Medical School, Dept. of Cell Biology
As an MD-PhD student in David Sabatini's lab, Rachel Wolfson identified Sestrin2 as a direct biochemical sensor for the amino acid leucine: when leucine binds Sestrin2, it is released from the GATOR2 complex, relieving a brake on mTORC1 and switching growth signalling on. It answered a question the field had chased for years — how a single amino acid's concentration gets converted into a growth signal.
Wolfson went on to identify KICSTOR, a complex that recruits GATOR1 to the lysosome and is required for nutrients to regulate mTORC1 at all, completing another structural piece of the pathway. She later trained in neurobiology and joined the Harvard Medical School faculty in 2024, where her lab now studies how sensory neurons detect signals from internal organs.
The timeline below follows her contributions gathered in this Atlas.
Milestones in the Atlas
| Year | Evidence | Study |
|---|---|---|
| 2015 | M | Sestrin2 is a leucine sensor for the mTORC1 pathway WOL2015 Identifies Sestrin2 as a direct leucine sensor for the mTORC1 pathway. |
| 2015 | M | Structural basis for leucine sensing by the Sestrin2-mTORC1 pathway SAX2015 Solves the crystal structure of Sestrin2 bound to leucine, revealing the molecular pocket that lets it act as mTORC1's dedicated leucine sensor. |
| 2017 | M | KICSTOR recruits GATOR1 to the lysosome and is necessary for nutrients to regulate mTORC1 WOL2017 Identifies KICSTOR, the complex that recruits GATOR1 to the lysosome and is required for nutrient signalling to mTORC1. |
| 2017 | R | The Dawn of the Age of Amino Acid Sensors for the mTORC1 Pathway WOLF2017 Review of the newly discovered amino-acid sensors feeding into mTORC1. |