J. Wade Harper
Co-discovered the F-box motif that links substrates to SCF ubiquitin ligases, and co-leads with Steven Gygi the BioPlex protein-interaction map, which contributed to the discoveries of the CASTOR and SAMTOR nutrient sensors
Bert and Natalie Vallee Professor of Molecular Pathology and Chair, Department of Cell Biology, Harvard Medical School (since 2003; chair since 2014) · faculty, Department of Biochemistry, Baylor College of Medicine (1988–2003) · postdoc, Harvard Medical School (Bert Vallee lab) · PhD in Chemistry, Georgia Institute of Technology (1984)
Harper Lab, Harvard Medical School (Boston, Massachusetts, USA) ↗ Lab lineagetrained under Bert L. Vallee → Bluesky@harperlabhms.bsky.social ↗ ORCID0000-0002-6944-7236 ↗
Portrait: Harper Lab, Harvard Medical School
Harper's contribution to two of the Atlas's mTORC1 nutrient-sensing papers came from the interactome side of the problem, not the sensing biochemistry itself. His group, working with Steven Gygi's mass-spectrometry lab, built BioPlex — a systematic map of human protein–protein interactions made by tagging thousands of individual proteins, pulling each one out of cells, and identifying everything that co-purifies with it. When the Sabatini lab wanted to know what else physically touches the GATOR2 amino-acid-sensing complex, they searched BioPlex rather than starting from scratch: two 'previously uncharacterized' genes turned up as GATOR2 interactors and became CASTOR1 and CASTOR2 (2016). A year later, mining an expanded version of BioPlex for GATOR1/KICSTOR partners flagged another orphan gene, later renamed SAMTOR (2017). In both cases, the Harper–Gygi interaction map is what handed the Sabatini lab the candidate protein before any of the nutrient-binding biochemistry began.
Harper trained as a chemist before moving into protein biochemistry as a postdoc with Bert Vallee at Harvard Medical School, then spent 15 years on the Baylor College of Medicine faculty. It was at Baylor, in 1996, that his group — working with Stephen Elledge's lab — identified the F-box, a short protein motif that lets 'substrate receptor' proteins dock onto the SCF (Skp1–Cullin1–F-box) ubiquitin ligase complex, explaining how the cell's protein-degradation machinery achieves substrate specificity across the cell cycle.
Harper returned to Harvard Medical School in 2003 (department chair since 2014). His lab has since built some of the field's key large-scale interactome and quantitative-proteomics resources (BioPlex among them) and used them to dissect the PARKIN ubiquitin ligase's role in clearing damaged mitochondria (mitophagy), work directly relevant to Parkinson's disease. He was elected to the American Academy of Arts and Sciences (2018) and the National Academy of Sciences (2023).
Milestones in the Atlas
A selection, not a full bibliography: only papers that meet the Atlas inclusion criteria.
| Year | Evidence | Study |
|---|---|---|
| 2016 | M | The CASTOR Proteins Are Arginine Sensors for the mTORC1 Pathway CHA2016 Co-built BioPlex, the immunoprecipitation-mass-spectrometry interactome dataset that first flagged the uncharacterized protein GATSL3 (CASTOR1) as a GATOR2 binding partner. |
| 2017 | M | SAMTOR is an S-adenosylmethionine sensor for the mTORC1 pathway GU2017 Co-built the expanded BioPlex interactome that, when mined for GATOR1/KICSTOR partners, flagged the uncharacterized protein C7orf60 — later renamed SAMTOR. |
Co-authors in the Atlas 12
People with a profile here who share at least one study with J. Wade Harper.
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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
- Robert A. Saxton 2 shared studies Solved, as a Sabatini-lab graduate student, the structures of the leucine sensor Sestrin2 and the arginine sensor CASTOR1, showing how each one grips its amino acid. He also co-wrote a widely cited 2017 review of mTOR signalling with David Sabatini
- Sonia M. Scaria 2 shared studies Contributed, as an MIT undergraduate in the Sabatini lab, to the discovery of CASTOR1 as the arginine sensor and SAMTOR as the SAM sensor of the mTORC1 pathway
- Steven P. Gygi 2 shared studies Mass-spectrometry scientist whose Harvard lab builds large-scale proteomics methods, including the BioPlex human protein-interaction map, and contributed proteomics to the discoveries of the CASTOR and SAMTOR nutrient sensors
- Grace Y. Liu Wrote with David Sabatini a major 2020 review of mTOR in nutrition, growth and ageing, and in the Sabatini lab studied how mTORC1 senses nutrients such as serine
- Gregory A. Wyant Showed that the lysosomal protein SLC38A9 exports leucine and other essential amino acids out of the lysosome, letting cells grow on proteins they have taken up and broken down there
- Jose M. Orozco Researcher trained in David Sabatini's laboratory at the Whitehead Institute and MIT who showed that mTORC1 senses glucose through the glycolysis metabolite DHAP
- Kendall J. Condon Ran genome-wide CRISPR screens revealing how mitochondrial stress signals to mTORC1
- Kuang Shen Solved, as a Sabatini-lab postdoc, cryo-EM structures of GATOR1 and of the FLCN–FNIP2–Rag–Ragulator complex, two switches that set mTORC1 activity. His UMass Chan lab studies the structural basis of nutrient sensing
- 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
- Tim Wang Co-developed genome-wide CRISPR screening in human cells (reported in parallel by Feng Zhang's lab) as a graduate student with David Sabatini and Eric Lander, and contributed to studies showing that the 4E-BPs mediate mTORC1's control of translation and that CASTOR1 senses arginine
- Xin Gu Cell biologist who discovered SAMTOR, the sensor that lets mTORC1 read the methyl donor SAM, as a PhD student at MIT, and who now leads a lab at Dana-Farber and Harvard Medical School studying ubiquitin-independent protein destruction by the midnolin-proteasome pathway
Every researcher with a profile →
On the programme
Meetings in the Atlas calendar where J. Wade Harper is listed among the speakers or organisers.
- past International Autophagy Conference 2026 (Norwegian, German & UK Networks) ↗ 25–27 May 2026 ·
Oslo, Norway · ★★ - past Keystone: Autophagy – Mechanisms to Therapy 2026 ↗ 2–5 Feb 2026 ·
Keystone, Colorado, USA · ★★
All meetings in the calendar →
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