Yi Liu
Drug-discovery scientist who builds selective kinase inhibitors, including the active-site mTOR inhibitor INK128
Chief Executive Officer, Kumquat Biosciences, San Diego · Co-founder and drug-discovery scientist, Intellikine, La Jolla · PhD; graduate training in the laboratory of Kevan M. Shokat
Kumquat Biosciences (San Diego, California, USA) ↗
Liu is the co-first author of the 2012 Nature paper on the translational landscape of mTOR signalling, sharing that position with Andrew Hsieh. On the paper itself the affiliation is Intellikine Inc. in La Jolla, the company side of the collaboration rather than the Ruggero laboratory at UCSF. The contribution was the compound: INK128, an ATP-competitive inhibitor that binds the catalytic site of mTOR directly.
That distinction is the point of the study. Rapamycin does not switch mTORC1 off; it blocks some substrates and largely spares others, in particular the phosphorylation of 4E-BP1, the protein that clamps down on the translation initiation factor eIF4E. An active-site inhibitor shuts down both mTORC1 and mTORC2, restores 4E-BP1's grip on eIF4E, and so silences the small set of pro-invasion messages - among them YB1, vimentin, MTA1 and CD44 - that ribosome profiling had shown oncogenic mTOR was selectively translating in prostate cancer cells.
Intellikine was founded out of Kevan Shokat's chemical-biology work, together with Zachary Knight and Pingda Ren, and built a series of PI3K and mTOR inhibitors; INK128 later entered clinical development as sapanisertib. Liu is now chief executive of Kumquat Biosciences in San Diego, where Pingda Ren is president and chief operating officer, working on small molecules against targets long considered undruggable.
Milestones in the Atlas
| Year | Evidence | Study |
|---|---|---|
| 2012 | M | The translational landscape of mTOR signalling steers cancer initiation and metastasis HSI2012 Co-first author on the industry side of the collaboration, responsible with the Intellikine team for developing and characterising INK128, the active-site mTOR inhibitor used to reverse the pro-invasion translation signature. |
Co-authors in the Atlas
People with a profile here who share at least one study with Yi Liu.
- Andrew C. Hsieh Showed, as first author in Davide Ruggero's lab, that oncogenic mTOR drives cancer metastasis by selectively translating a specific pro-invasion mRNA program
- 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
- Matthew R. Janes Showed, as first author in David Fruman's lab, that a dual TORC1/2 kinase inhibitor kills leukemia cells with much weaker effects on normal lymphocytes than rapamycin