Adem Kalender
Cell biologist who, in George Thomas's group at the University of Cincinnati, showed that metformin can switch off mTORC1 without AMPK by acting through the Rag GTPases
Department of Cancer and Cell Biology and Division of Hematology-Oncology, Metabolic Diseases Institute, University of Cincinnati (papers 2010–2011, at the time of the study)
Adem Kalender is first author of the Atlas study KAL2010, which asked how metformin, the most widely used diabetes drug, holds back cell growth. The usual explanation was that metformin lowers cellular energy, which switches on the energy sensor AMPK, which in turn shuts down mTORC1, the growth-control complex. Kalender and colleagues tested cells that lacked AMPK or the TSC1/TSC2 brake proteins. Metformin and its stronger relative phenformin still blocked mTORC1 in those cells. What the drugs needed instead were the Rag GTPases, small switch proteins that bring mTORC1 to the lysosome when nutrients are present.
The team checked the idea in two mouse settings, one for cancer and one for diabetes, and saw the same AMPK-independent effect. Together with a liver study by Foretz and colleagues from the same year, the paper moved part of metformin's action away from the AMPK route that textbooks gave it. The work was done in cells and mice, so it says how the drug can act, not how much of its benefit in patients runs through this route.
Kalender worked in George Thomas's laboratory at the University of Cincinnati's Metabolic Diseases Institute. With Thomas, Kalender also co-wrote two short commentaries in 2010 and 2011, one on how the bending of primary cilia feeds into TOR signalling and one on how the stress kinase p38 beta connects energy stress to mTORC1. No later publications or a current position could be confirmed, so the affiliation shown is the one on the Atlas paper.
Milestones in the Atlas
A selection, not a full bibliography: only papers that meet the Atlas inclusion criteria.
| Year | Evidence | Study |
|---|---|---|
| 2010 | M | Metformin, independent of AMPK, inhibits mTORC1 in a rag GTPase-dependent manner KAL2010 First author: showed in AMPK- and TSC-deficient cells and in mice that metformin and phenformin inhibit mTORC1 through the Rag GTPases rather than through AMPK. |
Co-authors in the Atlas 3
People with a profile here who share at least one study with Adem Kalender.
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- Benoit Viollet Showed that metformin still lowers liver glucose production without AMPK or LKB1, pointing instead to a drop in cellular energy charge
- George Thomas Purified and cloned S6K1, the kinase that became the classic readout of mTORC1 activity. His lab later showed that mice lacking S6K1 resist diet-induced obesity, and that amino acids signal to mTORC1 through the lipid kinase hVps34 (GUL2008)
- Sara C. Kozma Studies the S6K/mTOR pathway and how it controls cell growth, ribosome production, diabetes and cancer, including mTOR signalling in liver cancer.
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