Nathanael S. Gray
Medicinal chemist whose lab designed Torin1, an ATP-competitive mTOR inhibitor that blocks functions of mTORC1 that rapamycin misses. His lab is also known for covalent kinase inhibitors and targeted protein degraders
Krishnan-Shah Family Professor of Chemical and Systems Biology, Stanford University · previously Dana-Farber Cancer Institute / Harvard Medical School · PhD, UC Berkeley
Gray Lab, Stanford (Stanford, California, USA) ↗
Portrait: Gray Lab, Stanford University
Nathanael Gray is a chemical biologist whose lab designs small-molecule kinase inhibitors and, through long-running collaborations with mTOR biologists including David Sabatini's group, supplied some of the field's key chemical tools.
His lab developed Torin1, one of the first ATP-competitive mTOR inhibitors (reported in 2009 alongside compounds such as Kevan Shokat's PP242 and Ku-0063794), which block both mTORC1 and mTORC2 far more completely than rapamycin does. These inhibitors revealed a whole set of rapamycin-resistant mTOR functions — particularly in translation control — that catalytic-site inhibitors, but not rapamycin, could shut down, reshaping how the field defines 'full' mTOR inhibition.
The timeline below follows Gray's contributions gathered in this Atlas.
Milestones in the Atlas
A selection, not a full bibliography: only papers that meet the Atlas inclusion criteria.
| Year | Evidence | Study |
|---|---|---|
| 2009 | M | An ATP-competitive mammalian target of rapamycin inhibitor reveals rapamycin-resistant functions of mTORC1 THO2009 Co-develops an ATP-competitive mTOR inhibitor and shows it 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 Co-authors the discovery of DEPTOR, an mTOR inhibitor overexpressed in multiple myeloma and required for myeloma-cell survival. |
| 2011 | M | The mTOR-regulated phosphoproteome reveals a mechanism of mTORC1-mediated inhibition of growth factor signaling HSU2011 mTOR-dependent phosphoproteomics reveal Grb10 as a substrate mediating feedback inhibition of PI3K. |
| 2012 | M | A unifying model for mTORC1-mediated regulation of mRNA translation THO2012 Co-authors a unifying model for how mTORC1 regulates mRNA translation. |
Co-authors in the Atlas 13
People with a profile here who share at least one study with Nathanael S. Gray.
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- David M. Sabatini 4 shared studies Identified mTOR (as RAFT1) in 1994. His lab then mapped much of the machinery around it: raptor and rictor at the core of mTORC1 and mTORC2, the Rag–Ragulator system that docks mTORC1 on the lysosome, and the sensors that detect leucine, arginine and SAM
- Carson C. Thoreen 3 shared studies Used Torin1, one of the first ATP-competitive mTOR inhibitors, to reveal functions of mTORC1 that rapamycin cannot block. He then showed that mTORC1 controls translation of mRNAs for the protein-making machinery mainly through the 4E-BP proteins
- Seong A. Kang 3 shared studies Contributed to the Sabatini-lab studies that identified PRAS40 and DEPTOR, two of the cell's own mTOR inhibitors, and to the first characterisation of the mTOR inhibitor Torin1
- Timothy R. Peterson 2 shared studies Discovered DEPTOR, an inhibitor that binds mTOR in both complexes and is overexpressed in some multiple myelomas. He also showed that mTORC1 controls fat synthesis by regulating where the enzyme lipin 1 sits in the cell, and through it the SREBP pathway
- Kathleen Ottina Researcher in David Sabatini's lab at the Whitehead Institute and HHMI at MIT who contributed to studies of the GATOR1 amino acid off-switch, mTORC1 feedback on growth-factor signalling, and cancer drug resistance
- Lynne Chantranupong Showed as a Sabatini-lab graduate student that the Sestrins act through GATOR2 to regulate amino-acid signalling to mTORC1. She then discovered the CASTOR proteins, the cell's arginine sensors for the pathway
- Mathieu Laplante Co-wrote with David Sabatini one of the field's most cited reviews of mTOR in growth and disease, and his Laval lab studies how mTORC1 and DEPTOR control fat tissue and metabolism
- Michael B. Yaffe Cancer biologist and physician-scientist known for working out how phosphorylation creates binding sites on proteins, including the 14-3-3 family of phosphoserine/threonine-binding proteins, and how kinases choose their targets.
- Peggy P. Hsu Identified, in parallel with Yonghao Yu's group, Grb10 as an mTORC1 substrate that feeds back to dampen insulin and growth-factor signalling, and now studies the earliest steps of lung cancer as a physician-scientist
- Qingsong Liu Medicinal chemist in Nathanael Gray's lab who helped discover Torin1, an ATP-competitive mTOR inhibitor, and later built an independent kinase-inhibitor drug-discovery program in China
- Tim Wang Co-developed genome-wide CRISPR screening in human cells (reported in parallel by Feng Zhang's lab) as a graduate student with David Sabatini and Eric Lander, and contributed to studies showing that the 4E-BPs mediate mTORC1's control of translation and that CASTOR1 senses arginine
- W. Michael Kuehl Physician-scientist who spent decades working out the genetic and molecular biology of multiple myeloma and its precursor condition MGUS.
- Yasemin Sancak Showed as a Sabatini-lab graduate student, in parallel with Kun-Liang Guan's lab, that the Rag GTPases relay amino-acid signals to mTORC1, and that Ragulator anchors them to the lysosome where mTORC1 is switched on. She also identified PRAS40 as an insulin-regulated inhibitor of mTORC1
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