J. Wade Harper
Co-discovered the F-box motif that links substrate receptors to SCF ubiquitin ligases
PhD in Chemistry, Georgia Institute of Technology (1984) · postdoc, Harvard Medical School (Bert Vallee lab) · faculty, Department of Biochemistry, Baylor College of Medicine (1988–2003) · now Bert and Natalie Vallee Professor of Molecular Pathology and Chair, Department of Cell Biology, Harvard Medical School (since 2003; chair since 2014)
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
| 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. |
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 · Tier 2
- past Keystone: Autophagy — Mechanisms to Therapy 2026 ↗ 2–5 Feb 2026 · Keystone, Colorado, USA · Tier 2