Kun-Liang Guan
Mapped the upstream switches of mTOR
Born 1963, Zhejiang, China · University of Michigan → UC San Diego → Westlake University · MacArthur Fellow (1998)
Guan Lab, Westlake University ↗
Kun-Liang Guan grew up in Zhejiang, China, studied biology at Hangzhou University, and earned his PhD at Purdue. He won a MacArthur 'genius' Fellowship in 1998 and built his career at the University of Michigan and UC San Diego before returning to China to lead a lab at Westlake University.
Guan's lab worked out how signals reach mTOR from above. They showed that the tumour-suppressor complex TSC1/TSC2 acts as an off-switch by shutting down the small GTPase Rheb, and that the cellular energy sensor AMPK feeds into this control — explaining how growth factors, energy levels and stress all converge on mTOR. His team also helped define how amino acids and the Rag GTPases switch mTORC1 on. Separately, Guan is a leader of the Hippo pathway field, which controls organ size.
The timeline below follows Guan's mTOR-related discoveries collected in this Atlas.
Milestones in the Atlas
| Year | Evidence | Study |
|---|---|---|
| 2002 | M | TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling INO2002 Shows TSC2 is switched off by Akt — wiring insulin and growth-factor signals into the control of mTOR. |
| 2003 | M | Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling INOK2003 Identifies Rheb as the direct target of TSC2's GAP activity and a key activator of mTOR. |
| 2003 | M | TSC2 mediates cellular energy response to control cell growth and survival INO2003 Links cellular energy status, via AMPK, to TSC2 and the control of cell growth and survival. |
| 2006 | M | Identification of Sin1 as an essential TORC2 component required for complex formation and kinase activity YAN2006 Identified Sin1 as an essential TORC2 component required for Akt phosphorylation. |
| 2006 | M | TSC2 integrates Wnt and energy signals via a coordinated phosphorylation by AMPK and GSK3 to regulate cell growth INO2006 TSC2 integrates Wnt and energy signals through coordinated AMPK and GSK3 phosphorylation. |
| 2008 | M | Regulation of TORC1 by Rag GTPases in nutrient response KIM2008 Shows the Rag GTPases regulate TORC1 in response to nutrients. |
| 2008 | A | TSC-mTOR maintains quiescence and function of hematopoietic stem cells by repressing mitochondrial biogenesis and reactive oxygen species CHE2008 Showed why blood stem cells must keep mTOR LOW. Deleting TSC1 (which unleashes mTOR) drove resting stem cells into rapid division, flooded them with reactive oxygen species, and burned out their ability to self-renew. An antioxidant rescued them. A key link between mTOR, stem-cell exhaustion, and tissue aging. |
| 2011 | M | AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1 KIM2011 Revealed the tug-of-war over ULK1: the energy sensor AMPK phosphorylates ULK1 at activating sites to turn autophagy ON when energy is low, while mTORC1 phosphorylates a different site (Ser757) to keep it OFF and even blocks AMPK from reaching ULK1. Two opposing kinases wired to the same switch. |
| 2015 | M | Metabolism. Differential regulation of mTORC1 by leucine and glutamine JEW2015 Glutamine activates mTORC1 via a Rag-independent, Arf1-dependent route distinct from leucine. |
| 2019 | R | mTOR as a central hub of nutrient signalling and cell growth KIM2019 Review: mTOR as a central hub of nutrient signalling and cell growth. |