Kathleen Ottina
Researcher in David Sabatini's lab at the Whitehead Institute and HHMI at MIT who contributed to studies of the GATOR1 amino acid off-switch, mTORC1 feedback on growth-factor signalling, and cancer drug resistance
Whitehead Institute for Biomedical Research and Howard Hughes Medical Institute, MIT Department of Biology, Sabatini lab (papers 2011–2014, affiliation at the time of the studies) · current position not confirmed
Portrait: LinkedIn
Kathleen Ottina is a co-author on two Atlas papers from David Sabatini's lab. HSU2011 asked which proteins in a cell carry phosphate tags that depend on mTOR, the growth kinase. The team found that Grb10 is one of the proteins mTORC1 phosphorylates, and that Grb10 then damps signalling from insulin and growth factors through PI3K. This is a feedback loop: active mTORC1 turns down the signals that switch it on. The work was done in cultured cells.
BAR2013 found the off switch for the amino acid signal to mTORC1. A complex the lab named GATOR1 acts as a GAP for the Rag GTPases, a helper that makes these switch proteins turn themselves off when amino acids run low, while a second complex, GATOR2, opposes it. Some cancers carry mutations in GATOR1 genes; in those cell lines mTORC1 stayed on during amino acid starvation and the cells were very sensitive to rapamycin.
PubMed lists Ottina on two more papers from the same lab: a 2011 Genome Research RNAi screen for regulators of TORC1-S6K signalling in fruit-fly cells, and a 2014 Science Signaling study with Kris Wood's lab at Duke University that screened pathway-activating genes for those that let cancer cells survive targeted drugs, pointing to Notch1 in tamoxifen-resistant breast cancer. There Ottina is listed at the Whitehead Institute and the Howard Hughes Medical Institute in the MIT Department of Biology. A current position could not be confirmed.
Milestones in the Atlas
A selection, not a full bibliography: only papers that meet the Atlas inclusion criteria.
| Year | Evidence | Study |
|---|---|---|
| 2011 | M | The mTOR-regulated phosphoproteome reveals a mechanism of mTORC1-mediated inhibition of growth factor signaling HSU2011 Co-author on the mTOR-dependent phosphoproteome study that identified Grb10 as an mTORC1 substrate mediating feedback inhibition of growth-factor signalling. |
| 2013 | M | A Tumor suppressor complex with GAP activity for the Rag GTPases that signal amino acid sufficiency to mTORC1 BAR2013 Co-author on the cell study that identified GATOR1 as a GAP that switches off the Rag GTPases, and mTORC1, when amino acids are scarce. |
Co-authors in the Atlas 10
People with a profile here who share at least one study with Kathleen Ottina.
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- David M. Sabatini 2 shared studies 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
- Brian C. Grabiner Catalogued cancer-associated MTOR mutations and showed that many of them hyperactivate the kinase and can predict sensitivity to rapamycin; he also contributed to the discovery of GATOR1
- Liron Bar-Peled Showed as a Sabatini-lab graduate student that Ragulator switches the Rag GTPases on, acting as their GEF. He also discovered GATOR1 and GATOR2; GATOR1 switches the Rags off and its genes are mutated in some cancers
- Lynne Chantranupong Showed as a Sabatini-lab graduate student that the Sestrins act through GATOR2 to regulate amino-acid signalling to mTORC1. She then discovered the CASTOR proteins, the cell's arginine sensors for the pathway
- Matthew Meyerson Cancer geneticist whose group has helped identify key genes mutated in lung cancer, and who contributed the cancer-genome analysis to the discovery that GATOR1 is a tumour suppressor acting on mTORC1
- Michael B. Yaffe Cancer biologist and physician-scientist known for working out how phosphorylation creates binding sites on proteins, including the 14-3-3 family of phosphoserine/threonine-binding proteins, and how kinases choose their targets.
- 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
- Peggy P. Hsu Identified, in parallel with Yonghao Yu's group, Grb10 as an mTORC1 substrate that feeds back to dampen insulin and growth-factor signalling, and now studies the earliest steps of lung cancer as a physician-scientist
- 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
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