David A. Guertin
Built the mouse genetics that defined mTORC2's biological roles
PhD, UMass Chan Medical School · postdoc, Whitehead Institute/MIT (Sabatini lab) · Professor of Molecular Medicine, UMass Chan Medical School
Portrait: UMass Chan Medical School, Guertin Lab
David Guertin did his postdoctoral training in David Sabatini's lab, where he built mouse models lacking raptor, rictor or mLST8 in specific tissues to work out, organ by organ, which biological functions depend on mTORC1 versus mTORC2. This genetic dissection was essential to separating the two mTOR complexes' distinct roles in a living animal, not just in cultured cells.
Since joining the faculty at UMass Chan Medical School in 2009, Guertin has focused mTORC2 genetics on fat tissue and cancer, showing for instance that mTORC2 is required for prostate cancer driven by loss of the tumour suppressor Pten, and more recently studying how mTORC2 signalling shapes brown and white adipose tissue function.
The timeline below follows Guertin's contributions gathered in this Atlas.
Milestones in the Atlas
| Year | Evidence | Study |
|---|---|---|
| 2004 | M | Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton SAR2004 Discovery of Rictor and the SECOND mTOR complex, mTORC2. Crucially showed this complex is NOT blocked by rapamycin and does not use Raptor - it controls the cytoskeleton via PKC. This is the paper that split mTOR biology into 'two faces' at the molecular level. |
| 2006 | M | Ablation in mice of the mTORC components raptor, rictor, or mLST8 reveals that mTORC2 is required for signaling to Akt-FOXO and PKCalpha, but not S6K1 GUE2006 Uses tissue-specific mouse knockouts of raptor, rictor and mLST8 to show mTORC2 is required for cytoskeletal and metabolic functions distinct from mTORC1. |
| 2007 | R | Defining the role of mTOR in cancer GUE2007 Comprehensive review arguing mTOR signaling is commonly deregulated in human cancers, laying out the rationale for rapalog trials in oncology. |
| 2009 | A | mTOR complex 2 is required for the development of prostate cancer induced by Pten loss in mice GUE2009 Shows mTOR Complex 2 is required for prostate cancer driven by loss of the Pten tumour suppressor. |