Siraj M. Ali
Worked in the Sabatini lab on the papers that discovered raptor, mLST8 and rictor, and on the finding that the rictor-mTOR complex phosphorylates Akt. He later moved into cancer genomics and clinical diagnostics
Head of Translational Medicine, Lunit · previously Foundation Medicine and EQRx · graduate research, Sabatini lab, Whitehead Institute/MIT (co-author on the raptor, mLST8 and rictor papers)
Translational Medicine, Lunit (Seoul, South Korea) ↗
Portrait: The Pathologist Power List 2020
The 2002 and 2004 papers that identified raptor and rictor — the defining subunits of mTORC1 and mTORC2 — depended on mass-spectrometry protein identification carried out with Memorial Sloan Kettering Cancer Center's proteomics core, led by Hediye Erdjument-Bromage and Paul Tempst. Siraj Ali, working in David Sabatini's lab, was a co-author of these studies, which identified the previously unknown proteins that co-purified with mTOR.
This kind of unbiased biochemical purification — pulling down a protein of interest and mass-spectrometry-sequencing everything that comes with it — was the method that physically revealed mTORC1's and mTORC2's core subunits, well before genome-scale tools existed. It remains a template for how signalling complexes are discovered.
The studies below, gathered in this Atlas, mark that contribution.
Milestones in the Atlas
A selection, not a full bibliography: only papers that meet the Atlas inclusion criteria.
| Year | Evidence | Study |
|---|---|---|
| 2002 | M | mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery KIM2002 Co-author of the study that identified raptor, the defining subunit of mTORC1. |
| 2003 | M | GbetaL, a positive regulator of the rapamycin-sensitive pathway required for the nutrient-sensitive interaction between raptor and mTOR KIM2003 Discovered mLST8 (GbetaL), the third core subunit that clamps onto mTOR's kinase domain and stabilizes the complex. It fine-tunes how tightly Raptor holds mTOR in response to nutrients - a small but essential cog that later turned out to be especially critical for the mTORC2 complex. |
| 2004 | M | Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton SAR2004 Co-author of the study that identified rictor, the defining subunit of mTORC2. |
| 2005 | M | Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex SAR2005 The rictor-mTOR complex (mTORC2) directly phosphorylates Akt/PKB on Ser473, regulating cell survival. |
| 2006 | M | Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB SAR2006 The molecular explanation for rapamycin's dark side. Short-term rapamycin only hits mTORC1, but prolonged treatment can also inhibit the assembly of NEW mTORC2 in susceptible cell types, reducing mTORC2 abundance and cutting Akt signaling over time. The wording matters: this is prevention of new assembly, not the dismantling of complexes already built, and the response depends on cell context and length of exposure. This is the mechanistic root of the insulin-resistance side effect later shown in mice (see Lamming 2012) - crucial for anyone dosing rapamycin for longevity. |
Co-authors in the Atlas 10
People with a profile here who share at least one study with Siraj M. Ali.
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- David M. Sabatini 5 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
- Dos D. Sarbassov 5 shared studies Discovered rictor as a Sabatini-lab postdoc, in parallel with Michael Hall's lab, defining mTOR Complex 2, and showed that this complex is the long-sought kinase that phosphorylates Akt on serine 473. He also found that prolonged rapamycin treatment can block mTORC2 assembly
- Do-Hyung Kim 3 shared studies Co-discovered raptor, the defining partner of mTOR in mTORC1, and then mLST8 (GbetaL) as a Sabatini-lab postdoc. His Minnesota lab identified PRAS40 as an insulin-regulated link to mTORC1 and studies how mTORC1 controls autophagy
- Hediye Erdjument-Bromage 3 shared studies Ran the mass-spectrometry analyses in Paul Tempst's lab at Memorial Sloan Kettering that identified the unknown proteins in the raptor, mLST8 and rictor purifications, and contributed the same approach to work on how ERK inactivates TSC2
- Paul Tempst 3 shared studies Developed mass-spectrometry methods for identifying proteins from tiny samples, and led the Memorial Sloan Kettering proteomics laboratory that identified the unknown partners of mTOR in the raptor, mLST8 and rictor purifications
- Robert R. Latek 3 shared studies Bioinformatics scientist at the Whitehead Institute who worked on the Sabatini-lab papers that described raptor, mLST8 (GbetaL) and rictor (raptor and rictor were reported in parallel by other labs), the core partners of mTOR in its two complexes
- David A. Guertin 2 shared studies Built the mouse genetics that defined mTORC2's biological roles
- Andrew L. Markhard Contributed, as a Sabatini-lab researcher, to the discovery that Ragulator docks mTORC1 on the lysosome, and now studies metabolite signals that tell the body it has eaten
- 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
- Shomit Sengupta Showed that mTORC1 controls whether the liver makes ketone bodies during fasting, and now leads biology for drug discovery at a metabolic-disease biotech
Every researcher with a profile →
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