W. Michael Kuehl
Physician-scientist who spent decades working out the genetic and molecular biology of multiple myeloma and its precursor condition MGUS.
Deceased (1939–2023) · Senior Investigator, Genetics Branch, NCI Center for Cancer Research · Deputy Chief of the branch (2001–2006) · Retired 2015 · Waldenström Award, International Myeloma Workshop (2011)
Portrait: National Cancer Institute (public domain, via Wikimedia Commons)
Michael Kuehl was a physician-scientist who spent more than thirty years at the National Cancer Institute studying multiple myeloma, a cancer of antibody-producing plasma cells. He identified several mechanisms behind the disease and helped establish the link between the pre-cancer condition MGUS and myeloma, which matters for early diagnosis.
His expertise was central to the 2009 Cell paper in the Atlas, led by Timothy Peterson in David Sabatini's laboratory. The paper identified DEPTOR as a built-in brake on both mTOR complexes. In most cancers DEPTOR is low, but in a subset of myelomas with specific chromosomal translocations it is strongly overexpressed, and those cells need it to survive, because it keeps pro-survival Akt signalling active.
Kuehl died in April 2023. The NCI described him as someone who continued to advise colleagues in the Genetics Branch for several years after his retirement in 2015.
Milestones in the Atlas
A selection, not a full bibliography: only papers that meet the Atlas inclusion criteria.
| Year | Evidence | Study |
|---|---|---|
| 2009 | M | DEPTOR is an mTOR inhibitor frequently overexpressed in multiple myeloma cells and required for their survival PET2009 Co-author of the DEPTOR paper; his myeloma expertise supported the finding that some myeloma cells depend on high DEPTOR levels to survive. |
Co-authors in the Atlas 7
People with a profile here who share at least one study with W. Michael Kuehl.
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- Carson C. Thoreen Used Torin1, one of the first ATP-competitive mTOR inhibitors, to reveal functions of mTORC1 that rapamycin cannot block. He then showed that mTORC1 controls translation of mRNAs for the protein-making machinery mainly through the 4E-BP proteins
- David M. Sabatini Identified mTOR (as RAFT1) in 1994. His lab then mapped much of the machinery around it: raptor and rictor at the core of mTORC1 and mTORC2, the Rag–Ragulator system that docks mTORC1 on the lysosome, and the sensors that detect leucine, arginine and SAM
- Mathieu Laplante Co-wrote with David Sabatini one of the field's most cited reviews of mTOR in growth and disease, and his Laval lab studies how mTORC1 and DEPTOR control fat tissue and metabolism
- Nathanael S. Gray Medicinal chemist whose lab designed Torin1, an ATP-competitive mTOR inhibitor that blocks functions of mTORC1 that rapamycin misses. His lab is also known for covalent kinase inhibitors and targeted protein degraders
- Seong A. Kang Contributed to the Sabatini-lab studies that identified PRAS40 and DEPTOR, two of the cell's own mTOR inhibitors, and to the first characterisation of the mTOR inhibitor Torin1
- Timothy R. Peterson Discovered DEPTOR, an inhibitor that binds mTOR in both complexes and is overexpressed in some multiple myelomas. He also showed that mTORC1 controls fat synthesis by regulating where the enzyme lipin 1 sits in the cell, and through it the SREBP pathway
- Yasemin Sancak Showed as a Sabatini-lab graduate student, in parallel with Kun-Liang Guan's lab, that the Rag GTPases relay amino-acid signals to mTORC1, and that Ragulator anchors them to the lysosome where mTORC1 is switched on. She also identified PRAS40 as an insulin-regulated inhibitor of mTORC1
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