Zachary A. Knight
Neuroscientist whose lab studies the brain mechanisms behind appetite, thirst and body-temperature preference; he is a co-author of the 2009 study that introduced the TORKinibs PP242 and PP30.
Professor, Department of Physiology, UCSF · Investigator, Howard Hughes Medical Institute (named 2018) · Weill Institute for Neurosciences
Portrait: Knight Lab, UCSF
Zachary Knight is a professor of physiology at the University of California, San Francisco, a member of the UCSF Weill Institute for Neurosciences, and an investigator of the Howard Hughes Medical Institute, a title he received in 2018. His lab, called the Neurobiology of Homeostasis, studies how the brain controls appetite, thirst and the choice of a comfortable temperature.
FEL2009 was published in PLoS Biology with Morris Feldman as first author and Knight among the co-authors. The paper describes two new drugs, PP242 and PP30, that block the active site of the mTOR kinase. Unlike rapamycin, which only partly blocks mTORC1 and does not directly hit mTORC2, these drugs inhibit both complexes.
The authors used them to show that mTOR is needed for phosphorylation of Akt at S473, and that PP242 shuts down cap-dependent translation in conditions where rapamycin has no effect. A study from another group in the same year reached a similar conclusion, and together they showed that part of mTORC1 output is resistant to rapamycin.
Milestones in the Atlas
A selection, not a full bibliography: only papers that meet the Atlas inclusion criteria.
| Year | Evidence | Study |
|---|---|---|
| 2009 | M | Active-site inhibitors of mTOR target rapamycin-resistant outputs of mTORC1 and mTORC2 FEL2009 Co-author of the PLoS Biology study introducing the active-site mTOR inhibitors PP242 and PP30, which hit rapamycin-resistant outputs of mTORC1 and mTORC2. |
Co-authors in the Atlas 4
People with a profile here who share at least one study with Zachary A. Knight.
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- Davide Ruggero Showed that oncogenic mTOR signalling reprograms which mRNAs are translated, and that tumours become addicted to this through the 4E-BP–eIF4E axis. His UCSF lab found that mTOR-driven translation of a specific set of mRNAs promotes prostate cancer invasion and metastasis
- Kevan M. Shokat Co-developed the ATP-competitive 'TORKinib' mTOR inhibitors that block both mTORC1 and mTORC2, and later, with Neal Rosen's lab at Memorial Sloan Kettering, RapaLink-1, a third-generation inhibitor that overcomes mTOR resistance mutations
- Morris E. Feldman Chemical biologist who, in the Shokat lab at UCSF, introduced PP242 and the TORKinib class of drugs that block mTOR's active site and reach the outputs rapamycin misses
- Robbie Loewith Showed, as first author in Michael Hall's lab, that yeast TOR exists as two distinct complexes, the basis of the TORC1/TORC2 framework
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