David B. Shackelford
Cancer biologist at UCLA who studies lung tumours that have lost the LKB1 tumour suppressor, the upstream activator of AMPK, and who trained in Reuben Shaw's lab at the Salk Institute
Associate Professor, Division of Pulmonary and Critical Care Medicine, David Geffen School of Medicine at UCLA, and member, Jonsson Comprehensive Cancer Center · Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies (Reuben Shaw lab, papers 2008–2013)
Portrait: Shackelford Lab, UCLA
David Shackelford is a co-author of two Atlas papers from Reuben Shaw's lab at the Salk Institute that explain how AMPK, the cell's energy sensor, controls growth and recycling. GWI2008 found a second way AMPK shuts mTORC1 down. Besides activating the TSC2 brake, AMPK directly adds a phosphate group to Raptor, a core part of mTORC1, and this halts growth when energy runs low. EGA2010 showed that AMPK also adds phosphate groups to ULK1, the kinase that starts autophagy, which links low energy to the clearing of damaged mitochondria. Together the two papers describe a metabolic checkpoint: when fuel is short, the cell stops building and starts recycling.
The enzyme upstream of AMPK is LKB1, a tumour suppressor that is lost in many lung cancers. Shackelford's own work has followed that thread. A 2013 Cancer Cell paper from the Shaw lab, with Shackelford as first author, showed in mice that lung tumours lacking LKB1 respond to phenformin, a stronger relative of the diabetes drug metformin, because they cannot cope with the energy stress it causes.
At UCLA, Shackelford is an associate professor in pulmonary and critical care medicine. The lab uses genetically engineered mouse models of non-small cell lung cancer to study signalling and metabolism in tumours with KRAS and LKB1 mutations, tests compounds that selectively kill such tumours, and works on why LKB1-deficient tumours resist immune therapy. The American Lung Association has funded the lab through a Lung Cancer Discovery Award.
Milestones in the Atlas
A selection, not a full bibliography: only papers that meet the Atlas inclusion criteria.
| Year | Evidence | Study |
|---|---|---|
| 2008 | M | AMPK phosphorylation of raptor mediates a metabolic checkpoint GWI2008 Co-author of the study showing that AMPK directly phosphorylates Raptor to switch off mTORC1 when energy is low. |
| 2010 | M | Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy EGA2010 Co-author of the study showing that AMPK phosphorylates ULK1 to link energy sensing to autophagy and mitophagy. |
Co-authors in the Atlas 9
People with a profile here who share at least one study with David B. Shackelford.
ShowHide
- Dana M. Gwinn 2 shared studies First author of the 2008 study showing that the energy sensor AMPK switches off mTORC1 by phosphorylating raptor
- Daniel F. Egan 2 shared studies Showed as first author that AMPK directly phosphorylates ULK1, linking low cellular energy to autophagy and mitophagy, and contributed to the finding that AMPK brakes mTORC1 by phosphorylating raptor
- Maria M. Mihaylova 2 shared studies Studies how intestinal stem cells change with age and how diet shapes their metabolism
- Reuben J. Shaw 2 shared studies Showed, in parallel with two other groups, that the tumour suppressor LKB1 directly activates AMPK, and that AMPK brakes mTORC1 by phosphorylating raptor. His Salk lab also linked AMPK to autophagy through ULK1 and helped explain how metformin acts in the liver
- Benjamin E. Turk Kinase biochemist who studies how protein kinases choose their substrates; co-author on the discovery that AMPK phosphorylates raptor and on the study showing that mTORC1 sites differ in intrinsic substrate quality.
- Benoit Viollet Showed that metformin still lowers liver glucose production without AMPK or LKB1, pointing instead to a drop in cellular energy charge
- John M. Asara Mass-spectrometry specialist whose core facility supplied metabolomics and proteomics for several mTOR studies, including measurements of purine, pyrimidine and SAM metabolism downstream of mTORC1.
- Malene Hansen Showed in worms, alongside a 2007 report from Beth Levine's laboratory, that autophagy is required for dietary restriction to extend lifespan
- Mondira Kundu Physician-scientist who works out what the autophagy-initiating kinases ULK1 and ULK2 actually do when a cell runs short of fuel
Every researcher with a profile →
Thank you. That helps us know which pages have been read by someone who knows the work.
Thank you. We will check it and correct the page.
Thank you. Your answer was counted anonymously.